Immunogene therapy against mouse leukemia using B7 molecules

Cancer Gene Ther. 2000 Jan;7(1):144-50. doi: 10.1038/sj.cgt.7700099.

Abstract

B7 costimulatory molecules play an important role in T-cell activation. It is well known that tumor cells that express B7 molecules can elicit antitumor immunity, but little is known regarding which B7 molecule, B7-1 (CD80) or B7-2 (CD86), can do so more efficiently. To address this issue, we have introduced B7-1 or B7-2 into 8709 cells, a radiation-induced mouse myelocytic leukemic cell line, and have compared their potentials regarding the induction of antitumor immunity. Either B7-1- or B7-2-transduced monoclonal sublines, 8709/B7-1 or 8709/B7-2, respectively, diminished tumorigenicity in syngeneic C3H mice. Some reports have indicated that B7-1 is superior to B7-2 in the induction of antitumor immunity. Contrary to these results, the 8709/B7-2 lines are superior to the 8709/B7-1 lines in their capacity to induce antitumor immunity. In vivo depletion of lymphocyte subsets demonstrated that both CD4+ and CD8+ T cells were indispensable for B7-1- or B7-2-dependent antitumor immunity, whereas natural killer cells were not. These results suggest that in some circumstances, B7-2 molecule is more effective than B7-1 molecule in eliciting antitumor immunity.

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Antigens, CD / therapeutic use
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / immunology
  • B7-1 Antigen / therapeutic use
  • B7-2 Antigen
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COS Cells
  • Cancer Vaccines / immunology
  • Genetic Therapy*
  • Killer Cells, Natural / immunology
  • Leukemia / etiology
  • Leukemia / genetics
  • Leukemia / immunology
  • Leukemia / therapy*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Transduction, Genetic
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cancer Vaccines
  • Cd86 protein, mouse
  • Membrane Glycoproteins