Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/CTLA-4 costimulatory molecules

J Immunol. 1995 Mar 15;154(6):2794-800.

Abstract

We have examined the role of the B7-2 costimulatory molecule, a second ligand for CD28/CTLA-4 counter-receptors, in the induction of antitumor immunity. A plasmid containing murine B7-2 cDNA was transfected into the immunogenic mouse mastocytoma P815 of DBA/2 origin. In contrast to the lethal growth of the wild-type (wt) P815 tumor, B7-2-positive (B7-2+) P815 cells inoculated into syngeneic mice regressed, and immunization of mice with such tumor cells protected them against the challenge of wt P815 tumor. Depletion of CD8+, but not of CD4+, lymphocytes in vivo by specific Abs abolished the regression of B7-2+ P815 tumors. CD8+ cytolytic T cells could be generated from mice immunized with B7-2+ P815. They were found to be MHC class I-restricted and specific for the P815 tumor. In contrast, transfection of the B7-2 gene into the nonimmunogenic MCA102 fibrosarcoma of C57BL/6 origin induced neither tumor regression nor protective immunity. Co-expression on MCA102 cells of B7-2 together with the related costimulator B7-1 also failed to induce immunity to MCA102 tumor. Our results indicate that transfection of B7-2 into tumor cells can improve host response to some tumors, and that the effects seen are similar to those previously observed for B7-1.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD*
  • Antigens, Differentiation / immunology
  • B7-1 Antigen / genetics*
  • B7-2 Antigen
  • Base Sequence
  • CD28 Antigens / immunology
  • CTLA-4 Antigen
  • Female
  • Flow Cytometry
  • Genetic Therapy
  • Immunoconjugates*
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / therapy
  • Signal Transduction / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection / genetics*
  • Tumor Cells, Cultured / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Membrane Glycoproteins
  • Abatacept