Haematoporphyrin Based Photodynamic Therapy Combined with Hyperthermia Provided Effective Therapeutic Vaccine Effect against Colon Cancer Growth in Mice

Abstract

Photodynamic therapy (PDT) has become an attractive option used in tumor treatment via its direct tumoricidal activities or its immune-boosting activities. On the other hand, heat shock protein 70 has been found to be largely associated with the establishment of anti-tumor activities offered by hyperthermia treated tumor cells. In the present study, we found that injection of tumor-bearing mice with colon cancer cell line CT-26 treated with haematoporphyrin based photodynamic therapy (hematoporphyrin monomethyl ether based PDT, HMME-PDT) together with hyperthermia demonstrated the most effective therapeutic effects against tumor growth, followed by cells treated by hyperthermia alone. CT-26 cells treated only with HMME-PDT failed to provide any therapeutic effects, although significant cell death was induced by HMME-PDT. Compared to hyperthermia treatment, HMME-PDT induced more efficient surface localization of HSP70 on CT-26 cells which correlated with efficient activation of cytolytic CD8 T cells and with effective anti-tumor responses. Thus, our study demonstrated that the surface expression of HSP70 may play a more important role than the total expression or release of this molecule in the activation of immune responses. And our study offered a novel modified PDT approach to the treatment of tumor cells intrinsically low on HSP70 expression.