Dual antigen target based immunotherapy for prostate cancer eliminates the growth of established tumors in mice (155.3)

Abstract

Abstract Generation of antigen-specific CD8 T cells is considered optimal for an effective immunotherapy against cancer. Knowing that heterogeneity of prostate cancer limits the therapeutic benefit, we developed a recombinant adenovirus type 5 (rAd5) co-expressing a fusion of PSA (prostate-specific antigen) and PSCA (prostate stem cell antigen) genes. The selection of these genes is based on their restricted distribution within the prostate and their association with the development and progression of prostate cancer. Immunization of mice with rAd5 vector co-expressing PSA and PSCA antigens (Ad5-PSPA) simultaneously induces the expansion of anti-PSA, and anti-PSCA T cells as measured by intracellular cytokine staining for IFN-y. To analyze the impact on therapeutic efficacy of Ad5-PSPA vaccine against the tumor cells co-expressing cognate antigens (RM11-PSA/PSCA cells), injection of mice with Ad5-PSPA vaccine inhibited the growth of established tumors. Initially, the mice developed slow growing tumors and eventually upto 80% of the mice remain tumor free following immunization with Ad5-PSPA vaccine. These data provide useful information that antigen-specific effector T cells can be generated simultaneously and their additive anti-tumor effect has the ability to eliminate the growth of established tumors. Therefore, the immunotherapy approach of using the simultaneous targeting of dual antigens associated with prostate cancer may have important implications for human clinical trials.