CAR-T cell engineering strategies aimed at safe and effective targeting of solid tumors

Adoptive cell therapy based on chimeric antigen receptor-engineered T (CAR-T) cells has proven to be life-saving for many cancer patients. However, its therapeutic efficacy so far been restricted only a few malignancies, with solid tumors proving especially recalcitrant efficient therapy. Poor intra-tumor infiltration by and “T dysfunction” due an immunosuppressive microenvironment are key barriers against CAR-T success tumors. Furthermore, low level expression of CAR-directed tumor-associated antigens (TAA) in normal tissues can result “on-target off-tumor” cytotoxicity, raising potential safety concerns. Using our best-in-class TALEN®-based gene editing platform, we present here innovative engineering strategies that combat some the challenges posed development These allogeneic ‘Smart CAR-T’ designed integrate locus-specific synthetic genes respond cues localized tumor microenvironment. The subsequent these increases persistence anti-tumor activity while staying milieu. Thus, proof-of-concept study demonstrates feasibility developing improve targeting mitigating risks, encouraging us bring them clinic. No conflict interest.