Antitumor immunity after vaccination with B lymphoma cells overexpressing a triad of costimulatory molecules

J Natl Cancer Inst. 2003 Apr 2;95(7):548-55. doi: 10.1093/jnci/95.7.548.


Background: The costimulatory molecules B7-1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3) play pivotal roles in the activation of T cells. We investigated whether in vivo vaccination with lymphoma cells infected with a recombinant, nonreplicating fowlpox (FP) virus encoding this triad of costimulatory molecules (TRICOM) could stimulate lymphoma-specific immunity.

Methods: TRICOM-infected A20 B lymphoma cells were analyzed for expression of B7-1, ICAM-1, and LFA-3. Mice (10 per group) were vaccinated with irradiated A20 cells infected with either the TRICOM vector or the wild-type FP virus (WT-FP), challenged with live A20 tumor cells, and followed for survival. Mice with established A20 tumors were also treated with irradiated TRICOM-infected A20 cells. Survival curves were compared with the log-rank statistic. The mechanism of the antitumor effect was studied by in vivo depletion of CD4(+) and CD8(+) T cells and in vitro cytotoxicity assays. All statistical tests were two-sided.

Results: A20 tumor cells infected with TRICOM expressed high levels of B7-1, ICAM-1, and LFA-3. Mice vaccinated with irradiated TRICOM-infected A20 cells had prolonged survival relative to mice vaccinated with WT-FP-infected cells (80% versus 20% survival at 110 days; P<.001). In mice with established tumors, tumor growth was slower in those treated with TRICOM-infected tumor cells than in those treated with WT-FP-infected cells, and this treatment provided a survival advantage (P<.001). Depletion of CD4(+) or CD8(+) T cells reduced the antitumor immunity provided by the tumor cell-TRICOM vaccine, and lymphocytes from vaccinated mice displayed in vitro cytotoxic activity toward A20 cells.

Conclusions: Increasing expression of costimulatory molecules on B lymphoma cells by infection with a recombinant FP virus encoding B7-1, ICAM-1, and LFA-3 stimulates antitumor immune responses in vivo and may provide a novel strategy for treating patients with B-cell malignancies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • B7-1 Antigen / immunology*
  • CD58 Antigens / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / pharmacology*
  • Cytotoxicity Tests, Immunologic
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Engineering
  • Immunotherapy / methods*
  • Intercellular Adhesion Molecule-1 / immunology*
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic


  • Antigens, Neoplasm
  • B7-1 Antigen
  • CD58 Antigens
  • Cancer Vaccines
  • Intercellular Adhesion Molecule-1