STRONG IMMUNOGENIC POTENTIAL OF A B7 RETROVIRAL EXPRESSION VECTOR - GENERATION OF HLA-B7-RESTRICTED CTL RESPONSE AGAINST SELECTABLE MARKER GENES

The stimulation of a specific immune response is an attractive goal in cancer therapy. Gene transfer of costimulatory molecules and/or cytok ine genes into tumor cells and the injection of these genetically modi fied cells leads to tumor rejection by syngeneic hosts and the inducti on of tumor immunity, However, the development of host immune response could be either due to the introduced immunomodulatory genes or due t o vector components, In this study, human renal cell carcinoma cell li nes were modified by a retrovirus to express the co-stimulatory molecu le B7-1 together with the hygromycin/thymidine kinase fusion protein ( HygTk) as positive and negative selection markers, These B7-1-transduc ed renal cell carcinoma cell lines were able significantly to activate allogeneic T cell proliferation, The cytolytic activity of these T ce lls was determined by employing several transduced and nontransduced r enal cell carcinoma cell lines as targets, Evidence for a strong vecto r-specific T cell reactivity induced by the Hyg/Tk protein was obtaine d in autologous renal cell carcinoma systems, Antibody blocking experi ments as well as peptide binding assays demonstrated an HLA-B7-restric ted T cell response directed against both the Hyg and the Tk genes, Th us, the vector itself may mask the generation of immune reactivity aga inst tumor antigens and may even detract from it, Vectors with immunog enic potential may be useful for tumor vaccination via cross priming i n vivo, whereas antivector reactivities would be detrimental in situat ions where gene defects are being corrected and where long term expres sion of a therapeutic protein is required.