ression of Human Disseminated Tumor

nloaded irecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive hocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production imited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be odified by RNA electroporation without integration-associated safety concerns. To establish a safe m for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription ieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could ected up to a week after electroporation. Multiple injections of RNA CAR–electroporated T cells meregression of large vascularized flank mesothelioma tumors in NOD/scid/γc(−/−) mice. Dramatic tueduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been g in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated nti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes ng that autologous T cells from cancer patients can be engineered to provide an effective therapy disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are el approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that omplement the use of retroviral and lentiviral engineered T cells. This approach may increase the thermay c apeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Cancer Res; 70(22); 9053–61. ©2010 AACR.