Rs. Chamberlain et al., COSTIMULATION ENHANCES THE ACTIVE IMMUNOTHERAPY EFFECT OF RECOMBINANTANTICANCER VACCINES, Cancer research, 56(12), 1996, pp. 2832-2836
Activation of T lymphocytes in the absence of a costimulatory signal c
an results in anergy or apoptotic cell death. Two molecules capable of
providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have b
een shown to augment the immunogenicity of whole-tumor cell vaccines.
To explore a potential role for costimulation in the design of recombi
nant anticancer vaccines, we used lacZ-transduced CT26 as an experimen
tal tumor and beta-galactosidase (beta-gal) as the model tumor antigen
. Attempts to augment the function of a recombinant vaccinia virus (rV
V) expressing beta-gal by admixture wit rVV expressing murine B7-1 wer
e unsuccessful. However, a double recombinant vaccinia virus engineere
d to express both B7-1 and the model antigen beta-gal was capable of s
ignificantly reducing the number of pulmonary metastases when administ
ered to mice bearing tumors established for 3 or 6 days. Most importan
t, the double recombinant vaccinia virus prolonged the survival of tum
or-bearing mice. These effects were antigen specific. The related cost
imulatory molecule B7-2 was found to have a similar, although less imp
ressive enhancing effect on the function of a rVV expressing beta-gal.
Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV enc
oding a model antigen significantly enhanced the therapeutic antitumor
effects of these poxvirus-based, therapeutic anticancer vaccines.