CAR-CD44v6

CD44v6 is a promising CAR-T-cell therapy target in AML patients with DNMT3A mutations. Notably, treatment with decitabine resulted in increased CD44v6 expression on the cell surface of DNMT3A-mutant AML cells. This increase in CD44v6 expression facilitates improved recognition and targeting by CD44v6 CAR-T cells.

We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control...Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

Hypomethylating agents (HAMs) decitabine (Dec) and azacitidine (Aza) have been widely used to treat AML. The combination of Dec or Aza pretreated CD44v6 CAR-T with pretreated AML cells demonstrated the most potent anti-tumor ability against AML. Dec or Aza in combination with CD44v6 CAR-T cells is a promising combination therapy for AML patients.

P1/2, N=8, Terminated, AGC Biologics S.p.A. | N=58 --> 8 | Trial completion date: Jun 2023 --> Jun 2021 | Recruiting --> Terminated | Trial primary completion date: Jun 2023 --> Jun 2021; Inability to close the study in a clinically relevant time frame

We have developed a second generation, anti-CD44v6 CAR T cell (CD44v6CAR) that mediates potent cytotoxic and effector function against AML and MM in-vitro...Selective inhibition of matrix metalloproteinase-2 in the multiple myeloma-bone microenvironment. Oncotarget 8 , 41827-41840, (2017).