Enhancement of tumour response to photodynamic therapy by adjuvant mycobacterium cell-wall treatment

Mycobacterium cell-wall extract (MCWE) is a potent non-specific immunostimulant that elicits a local inflammatory response associated with antitumour activity. Tumour-localized administration of MCWE has been examined as an adjuvant to photodynamic therapy (PDT) mediated by the photosensitizers Photofrin, benzoporphyrin derivative monoacid (BPD), metatetrahydroxyphenylchlorin (mTHPC), or zinc(II)-phthalocyanine (ZnPc). A single MCWE treatment, given immediately after light treatment of murine EMT6 tumours, potentiates the curative effect of PDT. A similar enhancement of tumour response to Photofrin-based PDT is obtained with the live Bacillus CalmetteGuérin (BCG) vaccine. Despite differences in the kinetics/intensity of damage induction to tumour microvasculature and othercharacteristics underlying the mechanism of antitumour activity of Photofrin, BPD, mTHPC and ZnPc, there appear to be no marked differences in the therapeutic benefit of adjuvant MCWE therapy combined with the PDT mediated by these various photosensitizers. This may be related to the fact that MCWE elicits a wide range of immunomodulatory effects that could amplify and sustain the inflammatory /immune responses triggered by PDT. The enhancement of inflammatory effector cell activity is indicated by the increased infiltration of neutrophils and other myeloid cells at the expense of malignant cells found in the MCWE plus mTHPC-based PDT treatment group compared to the PDT-only group.