Untouched GMP-Ready Purified Engineered Immune Cells to Treat Cancer

摘要: Purpose: Engineering T cells with receptors to redirect the immune system against cancer has most recently been described as a scientific breakthrough. However, main challenge remains GMP-grade purification of selectively expressing introduced receptor in order reduce potential side effects due poorly or nonengineered cells. Experimental Design: In test novel strategy, we took advantage model γδT cell (TCR), naturally interfering endogenous TCR expression and designed optimal retroviral cassette achieve maximal interference chains. Following transduction, engineered characterized by high αβTCR were efficiently depleted anti-αβTCR beads. Next, validated for expression, function panel tumor lines primary tumors allo-reactivity. Engineered further two humanized mouse models. Results: The untouched enrichment translated into highly purified receptor-engineered strong antitumor reactivity both vitro vivo . Importantly, this approach eliminated residual allo-reactivity Our data demonstrate that even long-term suboptimal chains such resting cells, remained absent control preserved. Conclusions: We present method production ready be potentially applicable all receptor-modified if is far from complete. Clin Cancer Res; 21(17); 3957–68. ©2015 AACR