462327 T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Eradicate CD19 Lymphoma and Prevent Antigen Escape In Vivo

Thursday, November 17, 2016: 4:45 PM
Continental 7 (Hilton San Francisco Union Square)
Eugenia Zah1, Meng-Yin Lin1, Anne Silva2, Michael Jensen2 and Yvonne Chen1, (1)Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, (2)Seattle Children's Research Institute, Seattle, WA

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated clinical efficacy in the treatment of advanced cancers, with anti-CD19 CAR-T cells achieving up to 90% complete remission among patients with relapsed B-cell malignancies. However, a substantial fraction (>10%) of these patients eventually relapse due to antigen escape, a process by which tumors evade T-cell detection by eliminating expression of the targeted antigen. Here, we report the design and optimization of bispecific, OR-gate CARs that can trigger robust T-cell activation in response to target cells that present either CD19 or CD20, thus preventing malignant B cells from escaping T-cell therapy by simply losing CD19 expression. We demonstrate that optimized OR-gate CAR-T cells—but not conventional, single-input CD19 CAR-T cells—can eliminate pre-existing CD19 mutant tumors as well as prevent the spontaneous emergence of antigen-negative tumor growth in vivo. This technology presents an effective measure against antigen escape in CD19 CAR-T cell therapy that is fully compatible with current clinical practice and manufacturing processes.

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See more of this Session: Protein Engineering III: Therapeutics
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division