T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells
University of California, Los Angeles · Seattle Children's Hospital · +4 more institutions
Abstract
The adoptive transfer of T cells expressing anti-CD19 chimeric antigen receptors (CARs) has shown remarkable curative potential against advanced B-cell malignancies, but multiple trials have also reported patient relapses due to the emergence of CD19-negative leukemic cells. Here, we report the design and optimization of single-chain, bispecific CARs that trigger robust cytotoxicity against target cells expressing either CD19 or CD20, two clinically validated targets for B-cell malignancies. We determined the structural parameters required for efficient dual-antigen recognition, and we demonstrate that optimized bispecific CARs can control both wild-type B-cell lymphoma and CD19(-) mutants with equal…
Citation impact
- FWCI
- 28.77
- Percentile
- 100%
- References
- 46
Authors
5- EZEugenia Zah
University of California, Los Angeles
- MLMeng-Yin Lin
University of California, Los Angeles
- ASAnne Silva-Benedict
Seattle Children's Hospital, Regional Cancer Center
- MCMichael C. Jensen
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa, University of Washington, Fred Hutch Cancer Center, Seattle Children's Hospital
- YYYvonne Y. ChenCorresponding
University of California, Los Angeles
Topics & keywords
- Chimeric antigen receptor
- CD19
- Antigen
- CD20
- Adoptive cell transfer
- Cancer research
- Immunology
- B cell
- Good health and well-being