Pigmented melanoma has not been considered amenable to PDT because of the high attenuation of the treatment light by melanin. We have developed a novel treatment protocol, using optical clearing and a dual-photosensitizer (tumor cell and vascular targeting) that was successful in eradicating thin (<1mm) pigmented melanoma grown intradermally in immunodeficient mice. In immunocompetent mice, the same treatment resulted in time- and organ-dependent immune biomarker upregulation, eradicated tumors >4mm thick (far beyond the reach of the light to destroy tumor directly) and markedly increased survival. Further, subsequent re-challenge by i.v. injection of melanoma cells at 1 month post treatment resulted in no tumor formation, the tumor-specific immunity was transferrable to other mice and the response of bilateral tumor showed an abscopal effect. Direct imaging in a dorsal skin window chamber model showed immune cell infiltration into the tumor mass. Preliminary work has shown that anti-tumor response can be induced even in intraocular uveal melanoma, despite the immune-privileged status of the eye.
This phenomenon of “PhotoChemical Immune Stimulation” was then tested in other solid tumor models and using porphyrin-lipid nanoparticles (Porphysomes) that have shown high PDT efficacy in multiple preclinical tumor models. Again, marked upregulation of immune biomarkers was observed, even in tumors that are considered immunologically “cold”.
This new paradigm of oncologic PDT has potential both to improve the response of primary solid tumors and to address the major challenges of tumor progression and metastases.
Brian C Wilson, Princess Margaret Cancer Centre-University Health Network/University of Toronto, CA