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<title>B cell acute lymphoblastic leukemia relapse following CD19 CAR immune-pressure via de-differentiation and lineage switch | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>B cell acute lymphoblastic leukemia relapse following CD19 CAR immune-pressure via de-differentiation and lineage switch</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session II
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">12:00 – 1:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NCI</strong></p></div><div class="schedule__description"><p><strong>CANCER-9</strong></p></div></div></div></div><p><strong>FARE Award Winner</strong></p><h2>Authors</h2><ul><li>E Jacoby</li><li>H Qin</li><li>S Nguyen</li><li>Y Yang</li><li>CD Chien</li><li>K Welp</li><li>J Shern</li><li>TJ Fry</li></ul><h2>Abstract</h2><p>Novel treatments for acute lymphoblastic leukemia (ALL) are utilizing the patient’s T cells targeting surface molecules on the leukemic blasts. CD19 is a surface marker restricted to B cells and highly expressed on B cell ALL. CD19 has been targeted through genetically engineered chimeric-antigen receptor (CAR) T cells, and via bispecific CD3-CD19 antibodies, with reports of relapse via CD19 loss. We used a murine injectable pre-B ALL driven by an E2a:PBX transgene, which results in death of recipients within 21 days. Murine CD19 CAR treatment of ALL-bearing mice resulted in long-term remission with long persistence of T cells. However, late relapses occurred essentially in all CAR treated animals when followed up to 1 year, all with loss of CD19 expression, compatible with clinical reports. Relatively early relapses had a pre-B phenotype with isolated loss of CD19 but retained expression of B220, CD22 and CD127. Later relapses had loss of all the B cell surface markers, along with down regulation of B cell transcripts (such as EBF1 and PAX5) in the mRNA. These late relapses showed expression of cell surface markers compatible with a myeloid lineage (Gr1, Mac1), T cell or undifferentiated lineage (KIT, CD9), confirmed by RNA-sequencing. Isolated loss of CD19 was reversible upon in-vivo passage of leukemia, but lineage switch patterns were stable in-vivo. Our data demonstrates plasticity of leukemic cells under antigen-specific immune pressure, with de-differentiation and lineage switch. This novel escape mechanism is already seen in clinical trials.</p><p><strong>Scientific Focus Area</strong>: Cancer Biology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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