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<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="32937862">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://www.mdpi.com/resolver?pii=ph13090245"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=6383&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=32937862&amp;db=pubmed&amp;nlmid=101238453"
title="See full text options at MDPI"
data-ga-category="full_text"
data-ga-action="MDPI"
data-ga-label="32937862"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--res.mdpi.com-data-pubmed-linkout.png" alt="MDPI full text link"><span class="text">
MDPI
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/32937862/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=32937862&amp;db=pubmed&amp;nlmid=101238453"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="32937862"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/32937862/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/32937862/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="32937862" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F32937862%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="A5TX5i9KOvTE7rjEVrBKS6aTUhtM4p4VRSD2I8C6o6G81SpuyKeMmeGxslbYX0Cf"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
data-ga-action="select_collection"
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
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<h2 class="title">
Abstract
</h2>
<div class="abstract-content selected"
id="eng-abstract">
<p>
An armed antibody (antibody-drug conjugate or ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg<sup>®</sup>) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved and late-stage ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, and their design for applications beyond oncology, to make ADCs the magic bullet that Paul Ehrlich dreamed of.
</p>
</div>
<p>
<strong class="sub-title">
Keywords:
</strong>
ADC; antibodydrug conjugate; bioconjugation; cancer; combination therapies; linker; payload; resistance.
</p>
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<h2 class="title">
Conflict of interest statement
</h2>
<div class="statement">
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Alain Beck is an employee of Pierre Fabre, Charles Dumontet has received research funding from Roche and is a founder of Mablinks. All authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.</p>
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<div class="figures" id="figures">
<h2 class="title">
Figures
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data-image-height="400"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/a74a419826b4/pharmaceuticals-13-00245-g001.gif"
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<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Schematic representation of the first… </p></div>
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<strong class="figure-label">
<p> Figure 1 </p>
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<div class="figure-caption-contents"><p> Schematic representation of the first and second generation FDA-approved ADCs: Mylotarg <sup> ® </sup> ,… </p></div>
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Figure 1
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<div class="figure-caption-contents">Schematic representation of the first and second generation FDA-approved ADCs: Mylotarg<sup>®</sup>, Adcetris<sup>®</sup>, Kadcyla<sup>®</sup>, Besponsa<sup>®</sup>, Polivy<sup>®</sup> and Padcev<sup>®</sup>.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Scheme 1 </p>
</strong>
<div class="figure-caption-contents"><p> Mylotarg <sup> ® </sup> or Besponsa <sup> ®… </sup> </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Scheme 1 </p>
</strong>
<div class="figure-caption-contents"><p> Mylotarg <sup> ® </sup> or Besponsa <sup> ® </sup> mechanism of action: (1) binding to the specific… </p></div>
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<strong class="figure-label">
Scheme 1
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<div class="figure-caption-contents">Mylotarg<sup>®</sup> or Besponsa<sup>®</sup> mechanism of action: (1) binding to the specific antigen (Ag), followed by internalization of the ADC-Ag complex through a clathrin-dependent mechanism; (2) transfer to endosomes; (3) the acid-sensitive hydrazone of the linker is cleaved in early endosome and lysosome; (4) transfer of pro-calicheamycin into the lysosome; (5) cleavage of the disulfide bridge to give calicheamycin then (6) transfer of calicheamycin into the cytoplasm and (7) transfer of calicheamycin into the nucleus. (8) Alternatively to 7, transfer of calicheamycin into the cytoplasm then (9) diffusion of calicheamycin into neighboring cancer cells to obtain a cytotoxic bystander effect and (10) all the previous steps lead to cell death.</div>
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<div class="caption-wrap">
<strong class="figure-label">
<p> Scheme 2 </p>
</strong>
<div class="figure-caption-contents"><p> Kadcyla <sup> ® </sup> mechanism of action:… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Scheme 2 </p>
</strong>
<div class="figure-caption-contents"><p> Kadcyla <sup> ® </sup> mechanism of action: (1) binding on its specific HER2 Ag, followed… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Scheme 2
</strong>
<div class="figure-caption-contents">Kadcyla<sup>®</sup> mechanism of action: (1) binding on its specific HER2 Ag, followed by internalization of the T-DM1-HER2 complex by a clathrin-dependent mechanism; (2) transfer to the endosome then (3) to the lysosome; (4) complete trastuzumab digestion to release the active metabolite, LYS-MCC-DM1 and (5) transfer into the cytoplasm. (6) due to its charge at the physiological pH, the active metabolite is unable to cross the cell membrane, therefore it does not elicit any bystander killing effect, and transfer to tubulin. (7) All the preceding steps lead to HER2-positive cancer cell death.</div>
</figcaption>
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Scheme 3 </p>
</strong>
<div class="figure-caption-contents"><p> Adcetris <sup> ® </sup> , Polivy <sup> ®… </sup> </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Scheme 3 </p>
</strong>
<div class="figure-caption-contents"><p> Adcetris <sup> ® </sup> , Polivy <sup> ® </sup> or Padcev <sup> ® </sup> mechanism of action: (1) binding… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Scheme 3
</strong>
<div class="figure-caption-contents">Adcetris<sup>®</sup>, Polivy<sup>®</sup> or Padcev<sup>®</sup> mechanism of action: (1) binding to a specific Ag, followed by internalization of the ADC-Ag complex according to a clathrin-dependent mechanism; (2) transfer to the endosomes then (3) to the lysosomes; (4) linker cleavage in the lysosomes takes place between the peptide sequence (ValCit) and the self-immolative spacer (PAB); (5) transfer of MMAE into the cytoplasm; (6) MMAE can also be released before internalization, then (7) enter the targeted cell (or a nearby tumor cell) and (8) intracellular or extracellular MMAE release is followed by tubulin targeting. In parallel to 8, (9) diffusion of another MMAE in neighboring tumor cells not targeted by the ADC to obtain a bystander killing effect and (10) all the previous steps lead to tumor cell death.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/a3098a21d942/pharmaceuticals-13-00245-g002.gif"
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<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADCs with a drug-to-antibody… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADCs with a drug-to-antibody ratio (DAR) 2 generated through antibody engineering and… </p></div>
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Figure 2
</strong>
<div class="figure-caption-contents">Homogeneous ADCs with a drug-to-antibody ratio (DAR) 2 generated through antibody engineering and site-specific bioconjugation.</div>
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data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f003">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/eee8019f7905/pharmaceuticals-13-00245-g003.gif"
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC generated by deglycosylation… </p></div>
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC generated by deglycosylation (position Q295), in the presence of PNGase F,… </p></div>
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Figure 3
</strong>
<div class="figure-caption-contents">Homogeneous ADC generated by deglycosylation (position Q295), in the presence of PNGase F, followed by a bioconjugation mediated by transglutaminase (position 297). The azide immunoconjugate, in the presence of DBCO-linker-MMAE, allows the production of a homogeneous ADC with a DAR 2.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/b96476a0f023/pharmaceuticals-13-00245-g004.gif"
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<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
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<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR 4 obtained by complete reduction (TCEP) of all… </p></div>
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Figure 4
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<div class="figure-caption-contents">Homogeneous ADC with a DAR 4 obtained by complete reduction (TCEP) of all 4 interchain disulfide bridges followed by a site-specific bioconjugation reaction via a dibromomaleimide linker (DBM).</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<p> Figure 5 </p>
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<div class="figure-caption-contents"><p> Homogeneous SDC (scFv-drug conjugate) with… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5 </p>
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<div class="figure-caption-contents"><p> Homogeneous SDC (scFv-drug conjugate) with a DAR 1 obtained by reduction (TCEP) of… </p></div>
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Figure 5
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<div class="figure-caption-contents">Homogeneous SDC (scFv-drug conjugate) with a DAR 1 obtained by reduction (TCEP) of the C-terminal intrachain disulfide bridge followed by a site-specific bioconjugation reaction via a dithiophenylmaleimide linker (DSPh).</div>
</figcaption>
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<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR 4 comprising a biparatopic anti-HER2 antibody conjugated to… </p></div>
</div>
<figcaption id="figure-caption-8" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6
</strong>
<div class="figure-caption-contents">Homogeneous ADC with a DAR 4 comprising a biparatopic anti-HER2 antibody conjugated to a tubulysin derivative via a classical maleimidocaproic linker.</div>
</figcaption>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/1f1e08b8562a/pharmaceuticals-13-00245-g007.gif"
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><p> Immunoconjugates IgG(F8)-SS-DM1 and SIP(F8)-SS-DM1 with… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><p> Immunoconjugates IgG(F8)-SS-DM1 and SIP(F8)-SS-DM1 with a DAR 2, and formula of the payload… </p></div>
</div>
<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 7
</strong>
<div class="figure-caption-contents">Immunoconjugates IgG(F8)-SS-DM1 and SIP(F8)-SS-DM1 with a DAR 2, and formula of the payload DM1.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="10"
data-label-slug="figure-8">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/e53b5b97e446/pharmaceuticals-13-00245-g008.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-10"
role="button"
data-image-width="743"
data-image-height="415"
data-image-alt="Figure 8"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f008">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-10"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/b319200961d3/pharmaceuticals-13-00245-g008.gif"
alt="Figure 8" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="743">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="415">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 8 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 8 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC with a DAR 2 carrying talirine including a dimeric derivative of… </p></div>
</div>
<figcaption id="figure-caption-10" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 8
</strong>
<div class="figure-caption-contents">Homogeneous ADC with a DAR 2 carrying talirine including a dimeric derivative of pyrrolobenzodiazepine (PBD; SGN-1882).</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="11"
data-label-slug="figure-9">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/7369c2e48d72/pharmaceuticals-13-00245-g009.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-11"
role="button"
data-image-width="759"
data-image-height="218"
data-image-alt="Figure 9"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f009">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-11"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/5eba2f4c0fde/pharmaceuticals-13-00245-g009.gif"
alt="Figure 9" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="759">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="218">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 9 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADCs with a DAR… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 9 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADCs with a DAR 2 carrying tesirine including a dimeric derivative of… </p></div>
</div>
<figcaption id="figure-caption-11" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 9
</strong>
<div class="figure-caption-contents">Homogeneous ADCs with a DAR 2 carrying tesirine including a dimeric derivative of PBD (SGN-3199).</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="12"
data-label-slug="figure-10">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/a2bd1ce4d612/pharmaceuticals-13-00245-g010.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-12"
role="button"
data-image-width="723"
data-image-height="369"
data-image-alt="Figure 10"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f010">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-12"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/1556bb8ac5fb/pharmaceuticals-13-00245-g010.gif"
alt="Figure 10" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="723">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="369">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 10 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC carrying an anthracycline… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 10 </p>
</strong>
<div class="figure-caption-contents"><p> Homogeneous ADC carrying an anthracycline derivative (PNU-159682). </p></div>
</div>
<figcaption id="figure-caption-12" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 10
</strong>
<div class="figure-caption-contents">Homogeneous ADC carrying an anthracycline derivative (PNU-159682).</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="13"
data-label-slug="figure-11">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/20f2628b05cf/pharmaceuticals-13-00245-g011.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-13"
role="button"
data-image-width="765"
data-image-height="274"
data-image-alt="Figure 11"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f011">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-13"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/cae417ecaa4c/pharmaceuticals-13-00245-g011.gif"
alt="Figure 11" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="765">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="274">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 11 </p>
</strong>
<div class="figure-caption-contents"><p> HDP-101 formula, ADC with a… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 11 </p>
</strong>
<div class="figure-caption-contents"><p> HDP-101 formula, ADC with a DAR 2, resulting from the site-specific conjugation of… </p></div>
</div>
<figcaption id="figure-caption-13" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 11
</strong>
<div class="figure-caption-contents">HDP-101 formula, ADC with a DAR 2, resulting from the site-specific conjugation of an α-amanitin analog (HDP 30.2115) onto an anti-BCMA Thiomab via a cathepsine B-sensitive linker.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="14"
data-label-slug="figure-12">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/19445c6156ae/pharmaceuticals-13-00245-g012.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-14"
role="button"
data-image-width="742"
data-image-height="390"
data-image-alt="Figure 12"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f012">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-14"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/f946727ffe74/pharmaceuticals-13-00245-g012.gif"
alt="Figure 12" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="742">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="390">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 12 </p>
</strong>
<div class="figure-caption-contents"><p> Formula of mirvetuximab soravtansine, antifolate… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 12 </p>
</strong>
<div class="figure-caption-contents"><p> Formula of mirvetuximab soravtansine, antifolate R1 antibody conjugated to DM4 via a non-cleavable… </p></div>
</div>
<figcaption id="figure-caption-14" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 12
</strong>
<div class="figure-caption-contents">Formula of mirvetuximab soravtansine, antifolate R1 antibody conjugated to DM4 via a non-cleavable linker.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="15"
data-label-slug="figure-13">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/7b5c75dd3ae1/pharmaceuticals-13-00245-g013.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-15"
role="button"
data-image-width="788"
data-image-height="329"
data-image-alt="Figure 13"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f013">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-15"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/b456de901cdb/pharmaceuticals-13-00245-g013.gif"
alt="Figure 13" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="788">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="329">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 13 </p>
</strong>
<div class="figure-caption-contents"><p> Formula of depatuximab mafodotin and… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 13 </p>
</strong>
<div class="figure-caption-contents"><p> Formula of depatuximab mafodotin and Blenrep <sup> ® </sup> (belantamab mafodotin-blmf), antibodies conjugated to MMAF… </p></div>
</div>
<figcaption id="figure-caption-15" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 13
</strong>
<div class="figure-caption-contents">Formula of depatuximab mafodotin and Blenrep<sup>®</sup> (belantamab mafodotin-blmf), antibodies conjugated to MMAF via a non-cleavable linker.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="16"
data-label-slug="figure-14">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/bab18b9ec35b/pharmaceuticals-13-00245-g014.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-16"
role="button"
data-image-width="724"
data-image-height="375"
data-image-alt="Figure 14"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f014">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-16"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/7bac35b3c464/pharmaceuticals-13-00245-g014.gif"
alt="Figure 14" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="724">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="375">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 14 </p>
</strong>
<div class="figure-caption-contents"><p> SYD985 formula, anti-HER2 trastuzumab conjugated… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 14 </p>
</strong>
<div class="figure-caption-contents"><p> SYD985 formula, anti-HER2 trastuzumab conjugated to <i> seco </i> -DUBA via a cleavable linker sensitive… </p></div>
</div>
<figcaption id="figure-caption-16" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 14
</strong>
<div class="figure-caption-contents">SYD985 formula, anti-HER2 trastuzumab conjugated to <i>seco</i>-DUBA via a cleavable linker sensitive to cathepsin B.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="17"
data-label-slug="figure-15">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/53f9df5da33f/pharmaceuticals-13-00245-g015.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-17"
role="button"
data-image-width="737"
data-image-height="224"
data-image-alt="Figure 15"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f015">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-17"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/593f241634dc/pharmaceuticals-13-00245-g015.gif"
alt="Figure 15" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="737">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="224">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 15 </p>
</strong>
<div class="figure-caption-contents"><p> Trodelvy <sup> ® </sup> (sacituzumab govitecan or… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 15 </p>
</strong>
<div class="figure-caption-contents"><p> Trodelvy <sup> ® </sup> (sacituzumab govitecan or IMMU-132) formula, ADC with a DAR 7.6, resulting… </p></div>
</div>
<figcaption id="figure-caption-17" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 15
</strong>
<div class="figure-caption-contents">Trodelvy<sup>®</sup> (sacituzumab govitecan or IMMU-132) formula, ADC with a DAR 7.6, resulting from anti-TROP-2 antibody conjugation to SN-38 via an acid-sensitive cleavable linker.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="18"
data-label-slug="figure-16">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/1ecf96161e0c/pharmaceuticals-13-00245-g016.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-18"
role="button"
data-image-width="697"
data-image-height="291"
data-image-alt="Figure 16"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f016">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-18"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/d884832e0ee6/pharmaceuticals-13-00245-g016.gif"
alt="Figure 16" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="697">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="291">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 16 </p>
</strong>
<div class="figure-caption-contents"><p> Enhertu <sup> ® </sup> (fam-trastuzumab deruxtecan-nxki or… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 16 </p>
</strong>
<div class="figure-caption-contents"><p> Enhertu <sup> ® </sup> (fam-trastuzumab deruxtecan-nxki or DS-8201a) formula, ADC with a DAR 7.7, resulting… </p></div>
</div>
<figcaption id="figure-caption-18" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 16
</strong>
<div class="figure-caption-contents">Enhertu<sup>®</sup> (fam-trastuzumab deruxtecan-nxki or DS-8201a) formula, ADC with a DAR 7.7, resulting from anti-HER2 trastuzumab conjugation to exatecan DX-8951 via a linker sensitive to proteolysis.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="19"
data-label-slug="figure-17">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/7eb2ac2fed51/pharmaceuticals-13-00245-g017.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-19"
role="button"
data-image-width="729"
data-image-height="411"
data-image-alt="Figure 17"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f017">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-19"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/d4813685de34/pharmaceuticals-13-00245-g017.gif"
alt="Figure 17" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="729">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="411">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 17 </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> a </b> ) Formula of… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 17 </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> a </b> ) Formula of an ADC resulting from the conjugation of dexamethasone… </p></div>
</div>
<figcaption id="figure-caption-19" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 17
</strong>
<div class="figure-caption-contents">(<b>a</b>) Formula of an ADC resulting from the conjugation of dexamethasone onto an anti-CD163 mAb, with a DAR of 4. (<b>b</b>) Formula of an ADC resulting from the site-specific conjugation of fluticasone propionate onto an anti-CD74 IgG4 mutated mAb, with a homogeneous DAR of 2. (<b>c</b>) Formula of an ADC resulting from the conjugation of a dexamethasone analog onto anti-TNF-α adalimumab, with a DAR of 2 or 4.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="20"
data-label-slug="figure-18">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/d405338abd09/pharmaceuticals-13-00245-g018.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-20"
role="button"
data-image-width="770"
data-image-height="491"
data-image-alt="Figure 18"
data-pmc-id="PMC7558467"
data-figure-id="pharmaceuticals-13-00245-f018">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-20"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c00/7558467/95fa8461bdf0/pharmaceuticals-13-00245-g018.gif"
alt="Figure 18" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="770">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="491">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 18 </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> a </b> ) Formula of… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 18 </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> a </b> ) Formula of an ADC resulting from the stochastic conjugation of… </p></div>
</div>
<figcaption id="figure-caption-20" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 18
</strong>
<div class="figure-caption-contents">(<b>a</b>) Formula of an ADC resulting from the stochastic conjugation of dasatinib onto an optimized anti-CXCR4 mAb (HLCX) through a gluthathione sensitive linker, with an average DAR of 3. (<b>b</b>) Formula of an ADC resulting from the site-specific conjugation of a LXR agonist onto an anti-CD11a mutated mAb, with a homogeneous DAR of 2.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="21"
data-label-slug="figure-19">
<a class="figure-link"
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<p> Figure 19 </p>
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<div class="figure-caption-contents"><p> RG7861 formula, ADC with a… </p></div>
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<div class="figure-caption-contents"><p> RG7861 formula, ADC with a DAR 2, resulting from the site-specific conjugation of… </p></div>
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Figure 19
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<div class="figure-caption-contents">RG7861 formula, ADC with a DAR 2, resulting from the site-specific conjugation of rifalogue onto an anti-wall-teichoic acid (WTA) Thiomab via a cathepsine B-sensitive linker, targeting the surface of <i>Staphylococcus aureus</i>.</div>
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