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Leukemia. 2018 Feb;32(2):402-412. doi: 10.1038/leu.2017.302. Epub 2017 Sep 27.

A compound chimeric antigen receptor strategy for targeting multiple myeloma.

Author information

1
iCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA.
2
Department of Pathology, Stony Brook Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.
3
Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, Sichuan, China.
4
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau SAR, China.
5
Department of Internal Medicine, Stony Brook Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.

Abstract

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

PMID:
28951562
PMCID:
PMC5808076
DOI:
10.1038/leu.2017.302
[Indexed for MEDLINE]
Free PMC Article

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