Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines

Ronald S. Chamberlain, Miles W. Carroll, Vincenzo Bronte, Patrick Hwu, Steven Warren, James C. Yang, Michael Nishimura, Bernard Moss, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticle

Abstract

Activation of T lymphocytes in the absence of a costimulatory signal can result in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have been shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombinant anticancer vaccines, we used lacZ-transduced CT26 as an experimental tumor and β- galactosidase (β-gal) as the model tumor antigen. Attempts to augment the function of a recombinant vaccinia virus (rVV) expressing β-gal by admixture with rVV expressing murine B7-1 were unsuccessful. However, a double recombinant vaccinia virus engineered to express both B7-1 and the model antigen β-gal was capable of significantly reducing the number of pulmonary metastases when administered to mice bearing tumors established for 3 or 6 days. Most important, the double recombinant vaccinia virus prolonged the survival of tumor-bearing mice. These effects were antigen specific. The related costimulatory molecule B7-2 was found to have a similar, although less impressive enhancing effect on the function of a rVV expressing β-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV encoding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines.

Original languageEnglish (US)
Pages (from-to)2832-2836
Number of pages5
JournalCancer Research
Volume56
Issue number12
StatePublished - Jun 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chamberlain, R. S., Carroll, M. W., Bronte, V., Hwu, P., Warren, S., Yang, J. C., Nishimura, M., Moss, B., Rosenberg, S. A., & Restifo, N. P. (1996). Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines. Cancer Research, 56(12), 2832-2836.