Gene Transfer of the Co‐Stimulatory Molecules B7‐1 and B7‐2 Enhances the Immunogenicity of Human Renal Cell Carcinoma to a Different Extent

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Abstract
Stimulation of a specific antitumour immune response with recruitment and induction of T‐cell effector functions represents an attractive concept in human cancer therapy. Different cytokines and the B7 co‐stimulatory molecules are both able to provide proliferation and activation signals for T cells. In the present study, we first demonstrated the absence of both B7‐1 and B7‐2 expression in human renal cell carcinoma (RCC) cell lines. The lack of B7 expression was associated with a low or absent proliferative response of allogeneic and autologous T cells upon stimulation with tumour cells. In order to investigate the role of B7‐1 and B7‐2, the human RCC cell line, MZ1257RC, which expresses normal levels of adhesion molecules and major histocompatibility complex (MHC) class I surface antigens, was transfected with B7‐1 and B7‐2 expression vectors, respectively. The B7‐1‐ and B7‐2‐transduced MZ1257RC cells were potent stimulators of allogeneic and autologous T‐cell proliferation. B7‐2 transfectants were approximately two‐ to threefold more effective in the induction of primary T‐cell activation than B7‐1‐transduced cells. Interleukin (IL)‐12 synergized with the B7/CD28 interaction to enhance allogeneic T‐cell proliferation, independently of the B7 molecule transduced. In contrast, IL‐2 only co‐operatively increased T‐cell activation in the presence of B7‐2. Our results suggest the following: first, that co‐stimulatory molecules are required for efficient T‐cell responses directed against RCC; second, that B7‐2 appears to be a more potent stimulator of tumour immunity as compared to B7‐1; and third, that B7 molecules selectively co‐operate with different T‐cell stimulatory cytokines. The different activity of B7‐1 and B7‐2 molecules on the immunogenicity of RCC will have implications for the development and optimization of RCC‐specific cancer vaccines.