Human Prostate Stem Cell Antigen and HSP70 Fusion Protein Vaccine Inhibits Prostate Stem Cell Antigen-Expressing Tumor Growth in Mice

Abstract

Prostate stem cell antigen (PSCA) has been considered a potentially worthwhile target for prostate cancer therapy with its overexpression in both androgen-dependent and androgen-independent prostate cancers. However, PSCA is an autoantigen that can evoke immunological tolerance and hardly incite effective immunologic response. In this study, we sought to construct the fusion protein vaccines based on PSCA and heat shock protein 70 (HSP70) and to evaluate their immune responses and therapeutic efficacy. A series of recombinant proteins were prepared, and then, the male C57BL/6 mice were immunized subcutaneously by inoculation with RM-PSCA/Luc cells. The PSCA-specific cellular immune responses were monitored with ELISPOT and intracellular cytokines staining assay, and ELISA assay was used to detect humoral immune responses. The tumor growth was observed by in vivo bioluminescence imaging. The results showed that the mice vaccinated with PSCA-HSP could induce the PSCA-specific cellular and humoral immune responses. Tumor progression could be quantitatively monitored by in vivo bioluminescence imaging. Animal experiments showed that PSCA-HSP could inhibit the growth of PSCA-expressing tumors and prolong the survival time of vaccinated mice. This study supported and confirmed the potential of HSP70 as a chaperone for protein vaccines, and PSCA-HSP could be of potential value for prostate cancer treatment.

PSCA regulates IL‐6 expression through p38/NF‐κB signaling in prostate cancer

“…PCa has, like most cancers, an immunosuppressive tumor microenvironment. Dong et al found that immunization with PSCA protein could incite effective immunologic response, which inhibited the growth of PSCA expressing tumors and prolonged the survival time of mice.…”

Immunohistochemical expression of heat shock proteins, p63 and androgen receptor in benign prostatic hyperplasia and prostatic carcinoma in the dog

“…Unlike Hsp70 with established pro‐survival functions, the role of Hsp60 is more controversial with both pro‐survival and pro‐apoptotic functions reported . Several studies have focused on the implications of Hsp60 and Hsp70 during human prostate tumourigenesis and cancer progression, as well as on their usefulness as prognostic markers of PCa . The information obtained from these studies may provide the scientific basis for the design of antitumour treatments targeting HSPs in combination with conventional therapies, which could improve the survival of PCa patients in the next future .…”

Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target

“…Although no relevant vaccination has been approved for clinical application, numerous studies have demonstrated robust anti-tumor effects of various types of vaccines that contain HSP70, effectively stimulating cellular or even humoral immune responses. Peptide-based vaccines are relatively easy to manufacture and usually composed of the HSP70 protein integrated with tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs), such as melanoma-associated antigen gene (MAGE)-HSP70 (164-167), prostate stem-cell antigen (PSCA)-HSP70 (168), and Mela-HSP70 (169). Two studies produced a promising human papillomavirus 16 (HPV16) protein vaccine of E7-HSP70 that robustly induces E7-specific CD8 + T cell immune response and resulted in significant prophylactic and therapeutic effects against E7-expressing cervical cancer (170,171).…”