Autologe cellulaire therapie toont blijvende werkzaamheid en nieuwe doelen bij melanoom en solide tumoren

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.