Exploitation of photodynamic therapy-generated immune response in cancer immunotherapy

M Korbelik, Ph.D.

British Columbia Cancer Agency, Vancouver, Canada

AIM: Photodynamic therapy (PDT) is a regulatory approved clinical modality for the treatment of various cancerous and non-cancerous lesions. Its effectiveness, PDT owes to secondary antitumor effects elicited through the induced engagement of host inflammatory and immune responses. Rapid tumor destruction associated with the activation of complement, massive sequestration of inflammatory/immune effectors and profuse release of immune mediators creates an environment that is highly conducive for the development of robust antitumor immune responses. This prompted us to explore the potential of exploiting PDT for use as one of the components in cancer immunotherapy protocols. In this study, we have examined the prospects of combining PDT with natural killer (NK) cell-based adoptive immunotherapy. METHODS: SiHa (human cervical squamous cell carcinoma) and HT-29 cells (human colorectal adenocarcinoma) were implanted subcutaneously in NOD-scid mice. For PDT treatment, mice received Foscan (0.15 mg/kg) and 24 hours later the tumors were treated with light (25 J/cm2). Cultures of NK92MI cells (IL-2 transfected variant of human NK92 cell line) were expanded and either 2 or 5x107 were adoptively transferred per mouse. RESULTS: The adoptive therapy with NK92MI cells (which when used alone were not effective in controlling tumor growth) significantly improved the cures of PDT-treated SiHa and HT-29 tumors. Flow cytometry-based analysis revealed a higher percentage of peritumorally injected NK92MI cells in PDT-treated than in non-treated tumors. CONCLUSIONS: The findings of this study demonstrate that combining PDT with advanced protocols of NK cell-based adoptive immunotherapy is a feasible strategy for improved control of solid cancerous lesions.

KEY WORDS: NK cells, adoptive immunotherapy, human tumor xenografts.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Immunotherapy.