06.07.22

Overcoming CAR-Mediated CD19 Downregulation

Blanco B, Ramírez-Fernández A, Bueno C, et al. Overcoming CAR-Mediated CD19 Downmodulation and Leukemia Relapse with T Lymphocytes Secreting Anti-CD19 T-Cell Engagers. Cancer Immunology Research. 2022; 10 (4): 498 (doi: 10.1158/2326-6066.CIR-21-0853).

Engineered T cells designed to continuously secrete a CD19/CD3-directed bispecific T-cell engager antibody (STAb-T19) may more effectively prevent relapse of B-cell acute lymphoblastic leukemia than chimeric antigen receptor (CAR)-modified T cells. Research demonstrated that, compared with engineered T cells expressing a second-generation anti-CD19 CAR (CAR-T19), the STAb-T19 cells do a better job of inducing cytotoxicity, blocking leukemia escape in vitro, and preventing in vivo relapse. Investigators credit its superiority to the fact that STAb-T19 averts the CD19 downmodulation that occurs with anti-CD19 CAR-mediated interactions. Downmodulation allows CD19-negative cancer cells to emerge and dodge the immune response of engineered CAR-T19 cells. Absent this sequence of events, and in tandem with its continued antibody secretion, STAb-T19 is able to quickly and effectively eradicate leukemic cells, thus checking tumor progression and avoiding relapses associated with CAR-T19 treatment. Further research is needed, according to the study authors, to fully assess the therapeutic scope and safety profile of STAb-T19 cells in a clinical setting.

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