Gene transfer of the co-stimulatory molecules B7-1 and B7-2 enhances the immunogenicity of human renal cell carcinoma to a different extent

Stimulation of a specific antitumour immune response with recruitment and i nduction of T-cell effector functions represents an attractive concept in h uman cancer therapy. Different cytokines and the B7 costimulatory 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 B 7-2 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 o rder to investigate the role of B7-1 and B7-2, the human RCC cell line, MZ1 257RC, which expresses normal levels of adhesion molecules and major histoc ompatibility complex (MHC) class I surface antigens, was transfected with B 7-1 and B7-2 expression vectors, respectively. The B7-1- and B7-2-transduce d MZ1257RC cells were potent stimulators of allogeneic and autologous T-cel l proliferation. B7-2 transfectants were approximately two- to threefold mo re effective in the induction of primary T-cell activation than B7-1-transd uced cells. Interleukin (IL)-12 synergized with the B7/CD28 interaction to enhance allogeneic T-cell proliferation, independently of the B7 molecule t ransduced. In contrast, IL-2 only co-operatively increased T-cell activatio n in the presence of B7-2. Our results suggest the following: first, that c o-stimulatory molecules are required for efficient T-cell responses directe d 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 selective ly co-operate with different T-cell stimulatory cytokines. The different ac tivity of B7-1 and B7-2. molecules on the immunogenicity of RCC will have i mplications for the development and optimization of RCC-specific cancer vac cines.