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 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.
Jung
D
D
Johannes Gutenberg-Universität, III. Medizinische Klinik, Langenbeckstr. 1, 55101 Mainz, Germany.
Hilmes
C
C
Knuth
A
A
Jaeger
E
E
Huber
C
C
Seliger
B
B
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins