MACROPHAGE-DIRECTED IMMUNOTHERAPY AS ADJUVANT TO PHOTODYNAMIC THERAPYOF CANCER

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D-3-binding protein-dervived macrophage-a ctivating factor (DBPMAF) was examined using a mouse SCCVII tumour mod el (squamous cell carcinoma). The results show that DBPMAF can markedl y enhance the curative effect of PDT. The most effective DBPMAF therap y consisted of a combination of intraperitoneal and peritumoral inject ions (50 and 0.5 ng kg(-1) respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the tre ated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMA F therapy alone showed no notable effect on the growth of SCCVII tumou r. The PDT-induced immunosuppression, assessed by the evaluation of de layed-type contact hypersensitivity response in treated mice, was grea tly reduced with the combined DBPMAF treatment. These observations sug gest that the activation of macrophages in PDT-treated mice by adjuvan t immunotherapy has a synergistic effect on tumour cures. As PDT not o nly reduces tumour burden but also induces inflammation, it is propose d that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.