Development of nfP2X7-CAR-T-cell therapy for the treatment of ovarian cancer

Bandara V, Niktaras VM, Willett VJ, et al. Engineered CAR-T Cells Targeting the Non-Functional P2X Purinoceptor 7 (P2X7) Receptor as a Novel Treatment for Ovarian Cancer. Clinical and Translational Immunology. 2024; 13 (5) (doi: 10.1002/cti2.1512).

Researchers have identified a non-functional variant of the P2X purinocepter 7 (npP2X7) receptor as a promising target for chimeric antigen receptor (CAR) T-cell treatment in patients with ovarian cancer. The antigen is a strong candidate because it is robustly expressed on tumor cells and is necessary for their survival but is not found in high volumes on healthy tissues. To evaluate the cytotoxic impact, investigators engineered T cells that recognize and attack nfP2X7 and then observed their effects in OVCAR3 and other ovarian cancer cell lines, normal peritoneal cells, in vitro and in vivo models, and in patient-derived tissue explants. The findings point to significant anti-tumor activity of nfP2X7 CAR-T cells in vitro compared with un-transduced CD3-positive T cells and significant inhibition of OVCAR3 tumor growth in a xenograft murine model of ovarian cancer in vivo. Additional studies using patient-derived xenografts are needed to foster the development of nfP2X7-CAR-T-cell therapy for patients with ovarian cancer, the authors conclude.
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