Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies - PubMed
4 hours ago
- #CAR-T cells
- #Solid tumors
- #Tumor microenvironment
- CAR T-cell therapy has revolutionized hematologic oncology but remains largely ineffective against solid tumors.
- Solid tumors evade immune attack through antigen heterogeneity, a suppressive tumor microenvironment (TME), and physical barriers.
- Next-generation engineering strategies focus on multi-specific and logic-gated CARs to prevent antigen escape and enhance precision.
- Armored CAR constructs secrete immunomodulatory payloads or express dominant-negative receptors to reprogram the immunosuppressive stroma.
- Cooperative strategies target and remodel the TME, including cancer-associated fibroblasts, fibrotic extracellular matrix, abnormal vasculature, and suppressive myeloid cells.
- Early clinical signals are encouraging, but translation to solid tumors faces safety, manufacturing challenges, and limited predictive biomarkers.
- The review highlights translational priorities and pragmatic design principles for safer, manufacturable clinical candidates.
- A staged, biomarker-driven deployment of integrated platforms is proposed for meaningful clinical impact in solid tumors.