CELL INTELLIGENCE · 肿瘤细胞治疗研究

The year 2025 marked significant advances in autologous cellular therapy for melanoma and solid tumors, building on landmark regulatory approvals in 2024. Lifileucel, the first Food and Drug Administration-approved tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, demonstrated durable efficacy in the 5-year analysis of the C-144-01 trial, with an objective response rate (ORR) of 31.4% and prolonged responses in a heavily pretreated population. Real world data further supported its effectiveness, with higher ORR likely reflecting earlier lines of therapy and differences in patient selection. Preferentially expressed antigen in melanoma (PRAME)-targeted T-cell receptor (TCR) T-cell therapy (anzu-cel, IMA203) showed promising activity in a phase 1 study, with ORR of approximately 50% in checkpoint inhibitor refractory melanoma, durable responses, and manageable toxicity, validating PRAME as a high value target across multiple tumor types. Next-generation engineered TIL approaches emerged to address limitations of high-dose IL-2. OBX-115, an IL-2 independent TIL platform expressing membrane-bound IL-15 regulated by acetazolamide, demonstrated early clinical activity with ORR of 67% in initial phase 1 data. Additional strategies, including CRISPR-mediated gene editing and checkpoint disruption, highlight a shift toward programmable, self-sustaining cellular therapies. Personalized neoantigen-based therapies advanced with early clinical validation of adoptive T-cell platforms and mRNA vaccines, demonstrating immune activation and improved recurrence-free survival in melanoma. Finally, afamitresgene autoleucel (afami-cel), a MAGE-A4 directed TCR-T therapy, showed durable efficacy in synovial sarcoma and expanding activity across solid tumors, establishing proof of concept for TCR-T approaches. Collectively, these advances position autologous cellular therapy as an evolving standard of care in melanoma and a promising modality across solid tumors, with ongoing efforts focused on improving accessibility, overcoming resistance, and optimizing combinatorial strategies.