On May 13, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that an article has been published detailing the immuno-ablative mechanism of action of PV-10, the Company’s novel investigational drug for cancer (Filing, 8-K, Provectus Pharmaceuticals, MAY 13, 2016, View Source [SID:1234512346]).
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The article, titled, "Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity Via Activation of Dendritic Cells by the Release of High Mobility Group Box 1," appears as an advance publication in Oncotarget, an Open-Access journal, and can be accessed by visiting:
View Source
The article documents results of a multi-year, multidisciplinary translational medicine program led jointly by Shari Pilon-Thomas and Amod A. Sarnaik of Moffitt Cancer Center in Tampa, Florida. The authors report detailed data on the mode in which intralesional injection of PV-10 (rose bengal) selectively kills tumor cells and the immunologic signaling that results from tumor ablation, starting with release of High Mobility Group Box 1 (HMGB1, a Damage-Associated Molecular Pattern molecule released by dying cancer cells that can serve as an immunological adjuvant to promote phagocytosis, antigen-presentation, and dendritic cell activation). The authors then follow this signaling through antigen uptake and dendritic cell activation, T cell priming and activation in peripheral blood, and culminating in a tumor-specific immune response marked by T cell infiltration and regression of uninjected tumors.
Eric Wachter, CTO of Provectus, observed, "The Moffitt researchers have systematically documented each of the key steps in the immuno-oncology cycle described by Chen and Mellman in their landmark review article (Oncology Meets Immunology: the Cancer-Immunity Cycle. Immunity 2013; 39: 1-10). In an exemplary demonstration of translational medicine, this team identified important immunologic markers in model systems and verified key facets of these in clinical trial participants, and similarly identified other markers in clinical trial participants and substantiated these in mouse models. While a number of their main observations were previously reported at scientific meetings, these are presented here in detailed, integrated fashion for the first time."
Shari Pilon-Thomas of Moffitt, stated, "Concordance of tumor-specific T cells in peripheral blood of clinical trial participants and mice led us to look for triggers of T cell activation. Working back from these observations, we found that HMGB1 release was common in mouse and man after tumor ablation with PV-10. These results support PV-10 ablation and the resulting tumor necrosis as the upstream trigger for systemic anti-tumor response."
Wachter noted, "This paper is a watershed event in the development of PV-10, walking the reader through all the steps of immune activation after PV-10 injection, from immunogenic cell death and signaling via release of HMGB1, dendritic cell recruitment and infiltration into draining lymph nodes, activation of tumor-specific T cells, and killing of uninjected tumors upon infiltration by these T cells."
Wachter added, "This mechanism of action informed the design of the two active PV-10 clinical trials: NCT02288897 in patients with locally advanced cutaneous melanoma (melanoma limited to the skin) to test the hypothesis that PV-10 alone can produce a systemic immune response that translates to longer progression free survival (PFS); and NCT02557321 in patients with later stage melanoma to test whether combination of PV-10 with the recently approved systemic immunotherapy, pembrolizumab, can "induce and boost" an immune response against melanoma."