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Exploitation of Immune Response‐eliciting Properties of Hypocrellin Photosensitizer SL052‐based Photodynamic Therapy for Eradication of Malignant Tumors
Author(s) -
Korbelik Mladen,
Merchant Soroush,
Huang Naiyan
Publication year - 2009
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2009.00610.x
Subject(s) - photodynamic therapy , photosensitizer , immune system , immunotherapy , cytotoxic t cell , cancer research , fibrosarcoma , cd8 , lymph , medicine , in vitro , immunology , chemistry , pathology , biochemistry , organic chemistry
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.