Exploitation of Immune Response-eliciting Properties of Hypocrellin Photosensitizer SL052-based Photodynamic Therapy for Eradication of Malignant Tumors

A diaminophenyl derivative of hypocrellin B (SL052) has been developed as a photosensitizer for use in photodynamic therapy (PDT) of solid tumors. Testing SL052-PDT on mouse carcinoma and fibrosarcoma models revealed a typical response seen with clinically established photosensitizers featuring initial rapid tumor ablation with ensuing recurrence at rates dependent on photosensitizer/light doses. Elevated numbers of immune cells were found in lymph nodes draining SCCVII mouse squamous cell carcinomas treated by SL052-PDT (in particular T cells), and the accumulation of degranulating cytotoxic T cells was detected at the tumor-treated site. This indicates that a significant contribution to tumor cures is elicited by an antitumor adaptive immune response. Two different immunotherapy agents, γ-interferon and antibody blocking inhibitory FcγRIIB receptor, were both found to be highly effective in potentiating the curative effect of SL052-PDT with SCCVII tumors. Combining SL052-PDT with FcγRIIB-blocking antibody treatment caused a further increase in the number of cells in tumor-draining lymph nodes and in degranulating CD8⁺ cells, suggesting the amplification of the immune response induced by PDT. Vaccines consisting of SCCVII cells treated with SL052-PDT in vitro were effective in reducing growth of established subcutaneous SCCVII tumors. In conclusion, PDT mediated by SL052 is suitable to be integrated with various immunotherapy protocols.