IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: Enhancement by simultaneous B7-1 expression

Jay B. Rao, Ronald S. Chamberlain, Vincenzo Bronte, Miles W. Carroll, Kari R. Irvine, Bernard Moss, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticle

Abstract

A number of cytokines and costimulatory molecules involved in immune activation have recently been identified including IL-12, a heterodimeric cytokine that supports the development of cell-mediated immunity, and B7-1, a costimulatory molecule involved in the activation of T lymphocytes. We explored the use of these immunomodulants as molecularly defined adjuvants in the function of recombinant anticancer vaccines using a murine model adenocarcinoma, CT26, transduced with a model Ag, β-galactosidase (β-gal). Although IL-12 given alone to mice hearing tumors established for 3 days did not have consistent antitumor activity, a profound therapeutic effect was observed when IL-12 administration was combined with a recombinant vaccinia virus (rVV) encoding β-gal called VJS6. On the basis of the reported synergistic effects of IL-12 and the costimulatory molecule B7-1 (CD80) in vitro, we immunized mice with a double recombinant vaccinia encoding both the model tumor Ag and the costimulatory molecule B7-1, designated B7-1β-gal rVV. The adjuvant administration of IL-12 after immunization with this virus significantly enhanced survival in tumor-hearing animals. T cell subset depletions demonstrated that the in vivo activity of IL-12 was largely independent of CD4+ T lymphocytes, whereas the in vivo activity of a B7-1 rVV required both CD4+ and CD8+ T cells to elicit maximal therapeutic effect. To our knowledge, this is the first description of B7-1 and IL-12 cooperation in vivo and represents a novel strategy to enhance the efficacy of recombinant anticancer vaccines.

Original languageEnglish (US)
Pages (from-to)3357-3365
Number of pages9
JournalJournal of Immunology
Volume156
Issue number9
StatePublished - May 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rao, J. B., Chamberlain, R. S., Bronte, V., Carroll, M. W., Irvine, K. R., Moss, B., Rosenberg, S. A., & Restifo, N. P. (1996). IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: Enhancement by simultaneous B7-1 expression. Journal of Immunology, 156(9), 3357-3365.