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Article

Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma

1
Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2
Biology and Environmental Science College, Hunan University of Arts and Science, Changde 415000, China
3
Forevertek Biotechnology, Janshan Road, Changsha Hi-Tech Industrial Development Zone, Changsha 410205, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Cancers 2021, 13(5), 981; https://doi.org/10.3390/cancers13050981
Received: 22 January 2021 / Revised: 18 February 2021 / Accepted: 22 February 2021 / Published: 26 February 2021
(This article belongs to the Special Issue Immunotherapy, Tumor Microenvironment and Survival Signaling)
Chimeric antigen receptor (CAR) T cell therapy represents a major advancement in cancer treatment. Recently, FDA approved CAR-T cells directed against the CD19 protein for treatment of leukemia and lymphoma. In spite of impressive clinical responses with CD19-CAR-T cells, some patients demonstrate disease relapse due to either antigen loss, cancer heterogeneity or other mechanisms. Novel CAR-T cells and targets are important for the field. This report describes novel CD37, humanized CD37 and bispecific humanized CD37-CD19-CAR-T cells targeting both CD37 and CD19. The study demonstrates that these novel CAR-T cells specifically targeted either CD37 positive or CD37 and CD19-positive cells with endogenous and exogenous protein expression and provides a basis for future clinical studies.
CD19 and CD37 proteins are highly expressed in B-cell lymphoma and have been successfully targeted with different monotherapies, including chimeric antigen receptor (CAR)-T cell therapy. The goal of this study was to target lymphoma with novel CD37, humanized CD37, and bi-specific humanized CD37-CD19 CAR-T cells. A novel mouse monoclonal anti-human CD37 antibody (clone 2B8D12F2D4) was generated with high binding affinity for CD37 antigen (KD = 1.6 nM). The CD37 antibody specifically recognized cell surface CD37 protein in lymphoma cells and not in multiple myeloma or other types of cancer. The mouse and humanized CD37-CAR-T cells specifically killed Raji and CHO-CD37 cells and secreted IFN-gamma. In addition, we generated bi-specific humanized hCD37-CD19 CAR-T cells that specifically killed Raji cells, CHO-CD37, and Hela-CD19 cells and did not kill control CHO or Hela cells. Moreover, the hCD37-CD19 CAR-T cells secreted IFN-gamma against CD37-positive and CD19-positive target CHO-CD37, Hela-CD19 cells, respectively, but not against CD19 and CD37-negative parental cell line. The bi-specific hCD37-CD19 significantly inhibited Raji xenograft tumor growth and prolonged mouse survival in NOD scid gamma mouse (NSG) mouse model. This study demonstrates that novel humanized CD37 and humanized CD37-CD19 CAR-T cells specifically targeted either CD37 positive or CD37 and CD19-positive cells and provides a basis for future clinical studies. View Full-Text
Keywords: chimeric antigen receptor; CAR-T cells; CD37; CD19; immunotherapy; cell therapy; tumor antigen; lymphoma chimeric antigen receptor; CAR-T cells; CD37; CD19; immunotherapy; cell therapy; tumor antigen; lymphoma
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MDPI and ACS Style

Golubovskaya, V.; Zhou, H.; Li, F.; Valentine, M.; Sun, J.; Berahovich, R.; Xu, S.; Quintanilla, M.; Ma, M.C.; Sienkiewicz, J.; Huang, Y.; Wu, L. Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma. Cancers 2021, 13, 981. https://doi.org/10.3390/cancers13050981

AMA Style

Golubovskaya V, Zhou H, Li F, Valentine M, Sun J, Berahovich R, Xu S, Quintanilla M, Ma MC, Sienkiewicz J, Huang Y, Wu L. Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma. Cancers. 2021; 13(5):981. https://doi.org/10.3390/cancers13050981

Chicago/Turabian Style

Golubovskaya, Vita, Hua Zhou, Feng Li, Michael Valentine, Jinying Sun, Robert Berahovich, Shirley Xu, Milton Quintanilla, Man C. Ma, John Sienkiewicz, Yanwei Huang, and Lijun Wu. 2021. "Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma" Cancers 13, no. 5: 981. https://doi.org/10.3390/cancers13050981

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