Translational Therapeutics

British Journal of Cancer (2007) 96, 67–72. doi:10.1038/sj.bjc.6603508 www.bjcancer.com
Published online 5 December 2006

Potentiation of photodynamic therapy of cancer by complement: the effect of bold italic gamma-inulin

M Korbelik1 and P D Cooper2

  1. 1British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3
  2. 2Tumor Biology Group, Australian National University Medical School and The Canberra Hospital, Woden, ACT 2603, Australia

Correspondence: Dr M Korbelik, E-mail: mkorbelik@bccrc.ca

Revised 3 November 2006; Accepted 6 November 2006; Published online 5 December 2006.

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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 italic gamma-inulin and examined its effects on PDT response of mouse tumours. Intralesional italic 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 italic gamma-inulin was further enhanced by IFN-italic gamma pretreatment. Tumour C3 protein levels, already elevated after individual PDT or italic gamma-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant italic 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 italic 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 italic 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.

Keywords:

photodynamic therapy, complement system, italic gamma-inulin, CD 8 lymphocytes, mouse tumours