Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

Abstract

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 g-inulin and examined its effects on PDT response of mouse tumours. Intralesional g-inulin (0.1 mg mouse À1 ) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of g-inulin was further enhanced by IFN-g pretreatment. Tumour C3 protein levels, already elevated after individual PDT or g-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant g-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 g-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforingranzyme pathway. This study demonstrates that g-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.

Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

“…High numbers of degranulating CD8 þ cells were found in lesions regressing after PDT vaccine treatment and much lower numbers in the tumours within the same treatment group that exhibited a poor early responsive (progressing after vaccination). Elevated numbers of degranulating CD8 þ cells were also found in tumours treated by a regular (direct) PDT treatment (Korbelik and Cooper, 2007).…”

“…The procedure used was recently described in detail (Korbelik and Cooper, 2007). Briefly, tumours were excised at 3 days after vaccination, weighed, enzymatically disaggregated, and the obtained single cell suspensions counted and subjected to surface staining with antibodies for three-colour flow cytometry.…”

Photodynamic therapy for photochemists

“…A gentle treatment is thought to release some immune stimulant from the breakdown of cells dying in response to PDT. This could be a powerful approach if it can be appropriately harnessed, but is still at an early stage of development [44].…”

Potentiating Effect of .BETA.-Glucans on Photodynamic Therapy of Implanted Cancer Cells in Mice

“…Thus, blocking the receptors of the anaphylatoxins C3a and C5a (Korbelik et al 2004) or the depletion of neutrophils (Kousis et al 2007) both significantly decrease tumor cure rates induced by PDT. In contrast, adjuvant treatment with complement-activating agents enhances the therapeutic effect of PDT (Cecic et al 2005;Korbelik and Cooper 2007). β -Glucans induce a primed state of complement receptor type 3 (CR3, CD11b/CD18) that can trigger killing of iC3b-target cells e.g.…”