CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR MUTATED FORMS OF EPIDERMAL GROWTH FACTOR RECEPTOR FOR USE IN TREATING CANCER

摘要

Compositions, methods, and kits are provided for producing rejuvenated cytotoxic T cells (CTLs) specific for mutated neo-antigen epitopes expressed on cancerous cells, including epidermal growth factor receptor (EGFR) and KRAS neo-antigen epitopes. Antigenspecific CTLs are rejuvenated by reprogramming them into induced pluripotent stem cells (IPSCs) using Yamanaka factors and redifferentiating them back into CTLs while expanding their numbers. After redifferentiation, the IPSC-derived rejuvenated CTLs retain the antigen specificity of the original CTLs from which they were derived, but have the advantage of having longer telomeres and higher proliferative activity than the original CTLs. Pharmaceutical compositions comprising such IPSC-derived rejuvenated CTLs are useful for treating cancers expressing the mutated neo-antigen epitopes recognized by the original CTLs.