Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions - PubMed
3 hours ago
- #Solid Tumors
- #Cancer Immunotherapy
- #Adoptive Cell Therapy
- Adoptive cell therapy (ACT) shows transformative potential in cancer immunotherapy, with durable benefits in hematologic malignancies and growing application in solid tumors.
- Key ACT modalities for solid tumors include CAR-T cells, tumor-infiltrating lymphocytes (TILs), and TCR-engineered T cells (TCR-T), though translation faces challenges like antigen heterogeneity, immune evasion, and immunosuppressive tumor microenvironments.
- Major obstacles include inadequate T cell trafficking, limited persistence, functional exhaustion, treatment resistance, on-target off-tumor toxicity, and adverse events such as cytokine release syndrome.
- Emerging strategies to overcome barriers involve multi-antigen targeting, armored/logic-gated CAR designs, metabolic/cytokine engineering, locoregional delivery, and next-gen manufacturing with allogeneic and gene-edited products.
- Future directions emphasize biomarkers, tumor microenvironment profiling, personalized treatment, combination immunotherapy, and precision immuno-oncology to optimize patient stratification and therapeutic outcomes.