The stimulation of a specific immune response is an attractive goal in
cancer therapy. Gene transfer of co-stimulatory molecules and/or
cytokine genes into
tumor cells and the injection of these genetically modified cells leads to
tumor rejection by syngeneic hosts and the induction of
tumor immunity. However, the development of host immune response could be either due to the introduced immunomodulatory genes or due to vector components. In this study, human
renal cell carcinoma cell lines were modified by a retrovirus to express the co-stimulatory molecule B7-1 together with the
hygromycin/
thymidine kinase fusion
protein (HygTk) as positive and negative selection markers. These B7-1-transduced
renal cell carcinoma cell lines were able significantly to activate allogeneic T cell proliferation. The cytolytic activity of these T cells was determined by employing several transduced and nontransduced
renal cell carcinoma cell lines as targets. Evidence for a strong vector-specific T cell reactivity induced by the Hyg/Tk
protein was obtained in autologous
renal cell carcinoma systems. Antibody blocking experiments as well as
peptide binding assays demonstrated an HLA-B7-restricted T cell response directed against both the Hyg and the Tk genes. Thus, the vector itself may mask the generation of immune reactivity against
tumor antigens and may even detract from it. Vectors with immunogenic potential may be useful for
tumor vaccination via cross priming in vivo, whereas antivector reactivities would be detrimental in situations where gene defects are being corrected and where long term expression of a therapeutic
protein is required.