Potentiation of photodynamic therapy of cancer by complement: the effect of gamma-inulin.
Host response elicited by photodynamic therapy (PDT) of cancerous lesions is a critical contributor to the clinical outcome, and complement system has emerged as its important element. Amplification of complement action was shown to improve tumour PDT response. In search of a clinically relevant complement activator for use as a PDT adjuvant, this study focused on gamma-inulin and examined its effects on PDT response of mouse tumours. Intralesional gamma-inulin (0.1 mg mouse(-1)) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of gamma-inulin was further enhanced by IFN-gamma pretreatment. Tumour C3 protein levels, already elevated after individual PDT or gamma-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant gamma-inulin proved highly effective in reducing recurrence rates following PDT using four different photosensitisers (BPD, ce6, Photofrin, and mTHPC). At 3 days after PDT plus gamma-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforin-granzyme pathway. This study demonstrates that gamma-inulin is highly effective PDT adjuvant and suggests that by amplifying the activation of complement system, this agent potentiates the development of CTL-mediated immunity against PDT-treated tumours.
Korbelik
M
M
British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3. mkorbelik@bccrc.ca
Cooper
P D
PD
D000818:Animals; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology; D005434:Flow Cytometry; D007444:Inulin / Q000627:therapeutic use*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D003176:Complement C3; D052118:Lysosomal-Associated Membrane Protein 1; D017319:Photosensitizing Agents; D007444:Inulin