TY - JOUR
T1 - Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines
AU - Chamberlain, Ronald S.
AU - Carroll, Miles W.
AU - Bronte, Vincenzo
AU - Hwu, Patrick
AU - Warren, Steven
AU - Yang, James C.
AU - Nishimura, Michael
AU - Moss, Bernard
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 1996/6/15
Y1 - 1996/6/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8665522
AN - SCOPUS:9344263997
SN - 0008-5472
VL - 56
SP - 2832
EP - 2836
JO - Cancer Research
JF - Cancer Research
IS - 12
ER -