Synthetic M13 phage engagers expand CAR-T cell antigen recognition to overcome tumor heterogeneity - PubMed
5 hours ago
- #Tumor Heterogeneity
- #CAR-T Therapy
- #Bacteriophage Engineering
- Synthetic M13 bacteriophage-based bispecific engagers (BiPEs) enable CAR-T cells to recognize multiple tumor antigens and resist dysfunction, broadening antigen recognition to tackle tumor heterogeneity.
- BiPEs use SpyTag-SpyCatcher to conjugate single-chain antibodies against distinct tumor targets on phage pIII proteins, redirecting M13 phage-specific CAR-T (MCAR-T) cells to eliminate heterogeneous tumor subclones and remodel CAR-T function.
- In syngeneic glioblastoma models, BiPEs enhanced MCAR-T efficacy against antigenically diverse tumors, significantly prolonging survival compared to single-target CAR-T, with in vivo delivery via lipid nanoparticles generating functional CAR-T cells with multitargeting activity.