HPV based photodynamic therapy: a new approach for anti-cancer therapy (VAC12P.1019)

A new method of targeted photodynamic therapy (PDT) is proposed for potentiating anti-tumor immunity. Human papillomavirus (HPV) virus-like particles (VLPs) bind a broad range of tumor types both, in vitro and in vivo, but do not bind healthy, intact tissues. We have linked a photosensitizer dye, IR700, to the HPV VLPs and applied the dye-coupled particles (IR700-VLP) to tumor cells. When exposed to 690nm light, the bound conjugates induced immediate necrotic-like cell death in ovarian, lung, melanoma and cervical cancer cell lines in vitro, and in melanoma and lung tumors in vivo. We are currently expanding these studies to examine long-term tumor growth/survival and the generation of anti-tumor immunity in C57Bl/6 mice using the TC-1 tumor model, which expresses the HPV oncogenes, E6 and E7. This model allows us to track the T-cell responses generated against the HPV oncogenes, in both primary and metastatic tumor settings. Treatment with IR700-VLP and light exposure induced an influx of CD8+ and CD4+ T-cells into the treated tumors. Ex vivo cultures of whole tumor cell suspensions showed IFN-γ production in PMA/ionomycin-stimulated CD8+ and CD4+ T cells and to a lower extent without stimulation, suggesting that these T-cells may have been primed against the tumor antigens. Our data suggest that local anti-tumor immunity can be induced through the rapid tumor cell death caused by IR700, in conjunction with the ability of HPV VLP to induce an innate immune response.