A compound chimeric antigen receptor strategy for targeting multiple myeloma

K. H. Chen, M. Wada, K. G. Pinz, H. Liu, X. Shuai, X. Chen, L. E. Yan, J. C. Petrov, Huda Shafic Salman, L. Senzel, E. L.H. Leung, X. Jiang, Y. Ma

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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.

LanguageEnglish (US)
Pages402-412
Number of pages11
JournalLeukemia
Volume32
Issue number2
DOIs
StatePublished - Feb 1 2018

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Antigen Receptors
Multiple Myeloma
Antigens
T-Cell Antigen Receptor
Disease Eradication
Health Services Needs and Demand
Population
T-Lymphocytes
Recurrence
bis(3-bis(4-chlorophenyl)methyl-4-dimethylaminophenyl)amine
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Chen, K. H., Wada, M., Pinz, K. G., Liu, H., Shuai, X., Chen, X., ... Ma, Y. (2018). A compound chimeric antigen receptor strategy for targeting multiple myeloma. Leukemia, 32(2), 402-412. https://doi.org/10.1038/leu.2017.302

A compound chimeric antigen receptor strategy for targeting multiple myeloma. / Chen, K. H.; Wada, M.; Pinz, K. G.; Liu, H.; Shuai, X.; Chen, X.; Yan, L. E.; Petrov, J. C.; Salman, Huda Shafic; Senzel, L.; Leung, E. L.H.; Jiang, X.; Ma, Y.

In: Leukemia, Vol. 32, No. 2, 01.02.2018, p. 402-412.

Research output: Contribution to journalArticle

Chen, KH, Wada, M, Pinz, KG, Liu, H, Shuai, X, Chen, X, Yan, LE, Petrov, JC, Salman, HS, Senzel, L, Leung, ELH, Jiang, X & Ma, Y 2018, 'A compound chimeric antigen receptor strategy for targeting multiple myeloma' Leukemia, vol. 32, no. 2, pp. 402-412. https://doi.org/10.1038/leu.2017.302
Chen KH, Wada M, Pinz KG, Liu H, Shuai X, Chen X et al. A compound chimeric antigen receptor strategy for targeting multiple myeloma. Leukemia. 2018 Feb 1;32(2):402-412. https://doi.org/10.1038/leu.2017.302
Chen, K. H. ; Wada, M. ; Pinz, K. G. ; Liu, H. ; Shuai, X. ; Chen, X. ; Yan, L. E. ; Petrov, J. C. ; Salman, Huda Shafic ; Senzel, L. ; Leung, E. L.H. ; Jiang, X. ; Ma, Y. / A compound chimeric antigen receptor strategy for targeting multiple myeloma. In: Leukemia. 2018 ; Vol. 32, No. 2. pp. 402-412.
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