Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer - PubMed
6 hours ago
- #immunotherapy
- #CAR-T cell therapy
- #lung cancer
- Engineered inhalable nanoplatform using induced pluripotent stem cell-derived exosomes (IEXOs) to enhance CAR-T cell therapy against lung cancer.
- IEXOs display bispecific PD-1/mesothelin (MSLN) single-chain variable fragments (scFv) and are loaded with indole-3-propionic acid (IPA) for metabolic reprogramming.
- BIEXO@IPA demonstrated high tumor cell-specific uptake (79.3%) via nebulization in orthotopic lung cancer models.
- Treatment with BIEXO@IPA reduced tumor burden by 87.9% and achieved 80% survival at 80 days.
- BIEXO@IPA bridged PD-1+ T cells to MSLN+ tumor cells, expanding progenitor exhausted T (Tpex) cells and reducing regulatory T cells.
- Combined with CAR-T cells, BIEXO@IPA achieved 66.7% complete remission, 100% survival at 80 days, and 83.3% resistance to tumor rechallenge.
- Safety assessments showed minimal toxicity, indicating a clinically translatable strategy.
- Addresses CAR-T limitations in solid tumors through synergistic multimodal immunomodulation.