Development of chimeric antigen receptor cellular therapy targeting CD19 for the treatment of pediatric acute lymphocytic leukemia

Wednesday, October 26, 2011 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center	NCI	CLIN/CULT/AGING/DISPREV-17

Authors

• DW Lee
• JN Kochenderfer
• C Rader
• RJ Orentas
• CL Mackall

Abstract

Relapsed pediatric ALL remains a difficult therapeutic challenge. CARs are genetically engineered molecules that allow T cells to recognize and kill specific targets. CARs are expanded ex vivo using antigen-independent techniques, requiring large-volume apheresis, a problematic procedure in children. CD19 is found on >95% of ALL blasts. I developed antigen-specific techniques to expand CD19-specific CAR T cells using artificial APCs (aAPCs) expressing Fc receptor and co-stimulatory molecule, CD137L. I created an Fc-CD19 fusion protein that drives expansion by facilitating interaction between aAPC and CD19-CAR T cells. Transduced or untransduced T cells were expanded using this or the classical method (OKT3 and IL-2). Cytotoxicity and cytokine release assays against four CD19+ ALL cell lines demonstrated equal killing and similar production of IFNγ, TNFα, and IL-2. Four days after immunodeficient NOG mice were engrafted with the ALL cells, NALM6, 1x10^7 untransduced T cells or 3x10^6 CD19-CAR T-cells (transduced but not expanded) were injected. All treated mice cleared leukemia by seven days while Mock animals died of ALL in 21 days. These results demonstrate excellent in vivo activity of CD19-CAR T cells against ALL and that aAPCs and CAR-specific Fc fusion proteins provide a potential off-the-shelf reagent for antigen-specific expansion of T cells.

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