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

Scand J Immunol. 1999 Sep;50(3):242-9. doi: 10.1046/j.1365-3083.1999.00588.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • Carcinoma, Renal Cell / immunology*
  • Cell Line
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Kidney Neoplasms / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • T-Lymphocytes / immunology*
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Membrane Glycoproteins