Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7

Area of Science:

• Oncology
• Immunotherapy
• Cell Biology

Background:

• Chimeric antigen receptor (CAR)-T cell therapy offers a novel approach to cancer treatment by genetically modifying T cells.
• Identifying tumor-specific antigens for targeting multiple solid cancers remains a significant challenge in immunotherapy development.
• A dysfunctional variant of the P2X purinoceptor 7 (P2X7), termed nfP2X7, is expressed on various cancer cells but not healthy cells.

Purpose of the Study:

• To develop and evaluate a CAR-T cell construct targeting the nfP2X7 antigen for potential broad-spectrum cancer immunotherapy.
• To assess the efficacy of nfP2X7-targeted CAR-T cells against multiple solid tumor types in vitro and in vivo.

Main Methods:

• Development of a prototype human CAR-T construct engineered to target the nfP2X7 antigen.
• In vitro assessment of antigen-specific cytotoxicity against twelve solid cancer types.
• In vivo evaluation of CAR-T cell anti-tumor efficacy in xenograft mouse models of breast and prostate cancer.

Main Results:

• The nfP2X7-targeted CAR-T construct demonstrated antigen-specific cytotoxicity against twelve solid cancer types, including breast, prostate, lung, colorectal, brain, and skin cancers.
• Significant anti-tumor efficacy was observed in xenograft mouse models of breast and prostate cancer treated with nfP2X7-targeted CAR-T cells.
• nfP2X7 was confirmed as a broadly expressed tumor-associated antigen, absent on healthy cells.

Conclusions:

• nfP2X7 is a promising immunotherapy target due to its widespread expression on diverse solid tumors.
• nfP2X7-targeted CAR-T cells exhibit potent anti-tumor activity and represent a potential strategy for wide-spectrum immunotherapy against solid tumors.