Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma

Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma

Blog Article

Chimeric antigen receptor (CAR) T-cell based immunotherapy has become a promising treatment mainly for hematological malignancies.Following the major success of CD19-targeted CAR, new potential targets for other malignancies are required.As such, B-cell maturation antigen (BCMA) is an attractive tumor-associated antigen to be targeted in multiple myeloma (MM).

Herein, we aimed at assessing the function and optimal configuration of different BCMA-specific CAR, based on the same targeting moiety but with a different hinge and co-stimulatory domain.We compared their function to that of a previously characterized BCMA-CAR used g35 coupe fender in clinical trials.All constructs were expressed at high levels by primary human T cells and could trigger cytokine production and cytotoxicity upon co-culture with multiple myeloma targets.

Nonetheless, critical differences were observed in off-target activation, exhaustion, and activation marker expression and in vivo antitumoral activity mediated by these different constructs.Interestingly, we noted that CD8-based hinge, combined with a 4-1BB intracellular baseball scoreboards for sale domain, proved superior compared to IgG4-connecting regions, and/or a CD28-signaling moiety respectively.Overall, this study emphasizes the influence of CAR primary structure on its function and led to the identification of a highly efficient BCMA-specific CAR, namely H8BB, which displayed superior anti-tumoral activity both in vitro and long-term in vivo efficacy.