Exploitation of immune response-eliciting properties of hypocrellin photosensitizer SL052-based photodynamic therapy for eradication of malignant tumors.

Abstract

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.

• Authors: Mladen Korbelik, Soroush Merchant, Naiyan Huang
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2009 Nov-Dec Vol. 85 Issue 6 Pg. 1418-24 ISSN: 1751-1097 [Electronic] United States
• PMID: 19709384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents
• Quinones
• Perylene
• hypocrellin B

Topics

• Animals
• Cell Line, Tumor
• Combined Modality Therapy
• Head and Neck Neoplasms (drug therapy)
• Immunotherapy
• Mice
• Molecular Structure
• Perylene (analogs & derivatives, therapeutic use)
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Quinones (therapeutic use)