B4M3 CAR-T cell enhance antitumor activity and non-tumor toxicity in ovarian cancer
Chimeric antigen receptor (CAR) T cells have demonstrated promising therapeutic outcomes in hematologic malignancies, but efficacy against most solid tumors, including ovarian cancer (OC). To address CAR-T challenges, we generated CAR-T cells (B4M3 CAR-T) targeting two tumor-associated antigens, B7H3 and MSLN, simultaneously. Immunohistochemistry and proteomics technologies, were employed to analyze the xenograft tumor tissues and key organ tissues at the end of the treatment in vivo assays. B4M3 CAR-T cells demonstrated rapid antitumor effects under in vivo stress conditions, protected against organ damage, and exhibited favorable safety and tolerability. Molecular and signaling studies indicated that B4M3 CAR-T promoted tumor cell death by activating the NF-κB and TNF signaling pathways. Furthermore, B4M3 CAR-T cells enhancing the innate immune response and altering the metabolic profile. Collectively, our study successfully developed B4M3 CAR-T cells, which exhibited significant antitumor effects in ovarian cancer and it provide a novel strategy for the immunotherapy of OC.