PSCA CAR Vδ1 T cells: a safer off-the-shelf CAR T therapy for pancreatic cancer?

Pancreatic cancer remains among the deadliest malignancies, with a 5-year survival of ~13%. Chimeric antigen receptor (CAR) T -cell therapy offers hope, but conventional αβ T cells can trigger severe toxicities, including graft-versus-host disease (GvHD) when used for allogeneic therapy. By contrast, γδ T cells recognize tumors without MHCmajor histocompatibility complex restriction and are unlikely to cause GvHD, making them attractive candidates for "off-the-shelf" immunotherapy. Li et al engineered the Vδ1 subset of γδ T cells with a CAR targeting prostate stem cell antigen (PSCA) and compared these cells to CAR-engineered Vδ2 γδ and conventional αβ T cells in preclinical pancreatic cancer models. All three groups showed comparable tumor killing efficacy, but the CAR Vδ1 T cells induced none of the GvHD or systemic toxicity seen with CAR αβ T cells. They also displayed lower exhaustion than CAR Vδ2 cells, suggesting potential for greater persistence. Vδ1 CAR T cells could be expanded robustly ex vivo and remained highly potent even after cryopreservation, a key "off-the-shelf" requirement. These findings position CAR Vδ1 T cells as a safer alternative to traditional CAR T cells. Future rigorous clinical evaluation will be needed to confirm superior safety and efficacy of this promising approach in patients.
Cancer
Care/Management

Authors

Fraietta Fraietta, Lohmueller Lohmueller
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