A safety-modified SV40 Tag developed for human cancer immunotherapy
Stephanie S Tseng-Rogenski1, Mohamed S Arredouani2, June F Escara-Wilke1, Yilin C Neeley1, Michael J Imperiale3, Martin G Sanda1,2
1Department of Urology, School of Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 3Department of Microbiology and Immunology, School of Medicine, University of Michigan, Ann Arbor, MI, USA
Abstract: Simian virus 40 (SV40)-like DNA sequences have been found in a variety of human tumors, raising the possibility that strategies targeting SV40 may provide a potential avenue for immunotherapy directed against SV40 large T Antigen (Tag)-expressing tumors. We generated a recombinant vaccinia (vac-mTag) expressing mTag and herein assessed the ability of mTag to transform cells and to interact with anti-oncoproteins, as well as screened for the presence of potential HLA-A2.1-restricted epitopes within mTag. We found that transfection of cells with mTag did not lead to their transformation. Also, we demonstrated that mTag protein is degraded rapidly in cells. In addition, our work revealed that mTag did not physically interact with certain anti-oncoproteins. Finally, two potential HLA-A2.1-restricted functional epitopes within mTag sequence were identified. Our results show that mTag lacks the oncogenecity of full-length Tag and harbors potential HLA-A2.1-restricted immunogenic epitopes, hence suggesting the safety of vac-mTag for use in cancer immunotherapy.
Keywords: modified SV-40 T antigen, recombinant vaccinia, cancer immunotherapy