TY - JOUR
T1 - IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines
T2 - Enhancement by simultaneous B7-1 expression
AU - Rao, Jay B.
AU - Chamberlain, Ronald S.
AU - Bronte, Vincenzo
AU - Carroll, Miles W.
AU - Irvine, Kari R.
AU - Moss, Bernard
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 1996/5/1
Y1 - 1996/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0029885750&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029885750&partnerID=8YFLogxK
M3 - Article
C2 - 8617961
AN - SCOPUS:0029885750
SN - 0022-1767
VL - 156
SP - 3357
EP - 3365
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -