The research project concerns cancer gene therapy, primarily development of genetically modified viruses and T cells. 1) Oncolytic viruses are genetically modified to selectively replicate in and thereby kill tumor cells. We are primarily working with human adenovirus but also with vaccinia virus and Semliki forest virus. The project includes development of oncolytic viruses (design, construction, production) followed by various viral assays using cell lines, primary cultures and in vivo models. 2) T cells are genetically modified with a novel T cell receptor (TCR) or chimeric antigen receptor (CAR) so that they can target tumor-associated antigens and kill tumor cells. The project includes cloning of TCRs and CARs into lentiviral vectors for modification of T cells. It also includes analysis of the modified T cells using in vitro and in vivo models and optimizing the conditions for appropriate T cell stimulation.