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, gamma-interferon and antibody blocking inhibitory FcgammaRIIB receptor, were both found to be highly effective in potentiating the curative effect of SL052-PDT with SCCVII tumors. Combining SL052-PDT with FcgammaRIIB-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.
Korbelik
Mladen
M
British Columbia Cancer Agency, Vancouver, BC, Canada. mkorbelik@bccrc.ca
Merchant
Soroush
S
Huang
Naiyan
N
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D007167:Immunotherapy; D051379:Mice; D015394:Molecular Structure; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011809:Quinones / Q000627:therapeutic use*
D017319:Photosensitizing Agents; D011809:Quinones; D010569:Perylene; C064522:hypocrellin B