Rose Bengal and Co-Inhibitory Blockade Improve Anti-Tumor Immunity, Melanoma Regression

Source: NewsWise, December 2014

Newswise — Rose Bengal has been around for decades starting as a way to dye wool. Originally used in medicine as a stain for ophthalmologists, it has a solid safety record going back to the 1930s. Recently, oncologists have examined its efficacy against cancer, specifically melanoma.

Clinical trials have shown that a preparation of rose bengal produced by Provectus Biopharmaceuticals, known among researchers as PV-10, has induced regression of both injected lesions and uninjected bystander lesions in patients with melanoma, and tumor ablation with PV-10 has been shown to increase certain T-cell populations in patients’ peripheral blood. Provectus recently submitted a protocol for a phase 3 study to the FDA.

However, research suggests that there are additional approaches to using PV-10 as an anti-cancer drug. In a study recently reported at the 29th annual meeting of the Society for Immunotherapy of Cancer, a team from Moffitt Cancer Center measured whether IL PV-10 and co-inhibitory blockade could improve anti-tumor immunity and regression of melanoma in mice.

The presentation by Dr Shari Pilon-Thomas of the Moffitt Cancer Center, concludes that the new data “support combination therapy with IL PV-10 and co-inhibitory blockade.” The title was “Efficacy of Intralesional Injection with PV-10 in Combination with Co-Inhibitory Blockade in a Murine Model of Melanoma,” is available at http://www.pvct.com/publications/SITCposter2014.pdf.

The testing assessed response of injected and uninjected B16 melanoma tumors in mice receiving PV-10 alone or in combination with one of three agents designed for co-inhibitory blockade. The tested agents targeted either CLTA-4, PD-1 or PD-L1, the three most common clinical targets for co-inhibitory blockade. In each case, combination of PV-10 with co-inhibitory blockade led to improved tumor response and enhanced anti-tumor immunity of T-cells. Further testing with the anti-PD-L1 agent showed that these improvements could apply to both injected and uninjected tumors.

Eric Wachter, PhD and Chief Technology Officer of Provectus, said, “This important work further validates use of an intralesional therapy with a systemic immunotherapy, and solidifies our plans for a promising second path for development of PV-10. In addition to use as a single-agent therapy for cutaneous melanoma (the focus of our phase 3 study), these findings support commencement of clinical testing of PV-10 in combination anti-CLTA-4, anti-PD-1 or anti-PD-L1 agents. We are assessing strategies to allow this work to commence in a timely and cost-effective manner so that we can begin translating these model test results into human clinical data.”

Combination therapies are grabbing not just headlines but also the attention of big pharma as well. Pfizer and Merck have gone so far as to begin a joint study of Pfizer’s crizotinib (XALKORI®) with Merck’s investigational anti-PD-1 antibody pembrolizumab, in a Phase 1b clinical study. With PV-10 entering a phase 3 trial as an intralesional treatment for melanoma, and with results Dr. Pilon-Thomas and her team announced at SITC, the future for rose bengal as an anti-cancer drug, either on its own or in combination with another drug, looks rosy indeed.

About Provectus Biopharmaceuticals, Inc.
Provectus Biopharmaceuticals, Inc., specializes in developing oncology and dermatology therapies. PV-10, its novel investigational drug for cancer, is designed for injection into solid tumors (intralesional administration), thereby reducing potential for systemic side effects. Its oncology focus is on melanoma, breast cancer and cancers of the liver. The Company has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications. PH-10, its topical investigational drug for dermatology, is undergoing clinical testing for psoriasis and atopic dermatitis. Provectus has completed phase 2 trials of PV-10 as a therapy for metastatic melanoma, and of PH-10 as a topical treatment for atopic dermatitis and psoriasis. Information about these and the Company’s other clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company’s website at http://www.pvct.com

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