“PV-10 might offer the perfect way to prime the immune system”

Two articles on PV-10, and Provectus and Moffitt ASCO 2014 posters came out today: Provectus outlines path forward for PV-10 and PV-10 produced complete response in 50% of advanced melanoma patients. The articles are variations on the same themes and quotes.

For a moment, think about this verbiage: "The study showed that following intralesional PV-10, both PV-10-injected and uninjected study lesions had pathologic complete response (pCR) in four of the eight patients and that all eight patients exhibited at least partial regression of the injected lesion," and "It is noteworthy that six of eight patients had metastatic disease refractory to previous ipilimumab, anti PD-1 and/or vemura[f]enib therapy." Said another way, perhaps, Moffitt achieved 100% "objective response" in injected lesions and at least 50% in uninjected lesions (there is no mention in the article about whether there was partial regression in the uninjected lesions of the four patients who did not achieve pCR.

Interestingly, Moffitt's Dr. Jeffrey Weber, M.D., Ph.D. said “This data provides more and more evidence that you are altering both local and systemic immunity in a positive way. It also provides a rationale for combination trials of PV-10 with check point protein inhibitors, such as ipilimumab, pembrolizumab and nivolumab. PV-10 might offer the perfect way to prime the immune system” {bold emphasis is mine}.

In April 2014 Dr. Weber said: "“Checkpoint inhibitors are quickly becoming the standard of care for metastatic melanoma, but 50 to 60% percent of patients do not benefit from these agents." The relevancy of PV-10 and other intralesional ("IL") agents to metastatic disease is their potential to make the combination (of the intralesional agent and the checkpoint inhibitor) better for patient in terms of efficacy, safety and tolerability, presumably more so than combinations of checkpoint inhibitors and other checkpoint inhibitors, or drug XYZ and drug ABC.

For example: "The combination of anti-CTLA-4 immunotherapy with agents that prime immune responses have been successfully employed in multiple tumor models and highlight the importance of immune priming for successful anti-CTLA-4 immunotherapy" (Source: Joseph Grosso and Maria Jure-Kunkel, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 2013). Or: "An immune system primed to properly identify and destroy tumor cells would eliminate errant cells in nearby lymph nodes and distant metastases, thus solving one of the most difficult problems in cancer therapy—the treatment of patients with late-stage disease (stage III or IV)" (Source: Jedd Wolchok, Memorial Sloan-Kettering Cancer Center, 2008). Or the 32 times "priming" is mentioned in Combining immunotherapy and targeted therapies in cancer treatment (Matthew Vanneman and Glenn Dranoff, Nature, 2012).

IL agents can prime the immune system. See PV-10 & Amgen's Talimogene Laherparepvec  (June 9, 2014) under the blog's News tab. According to Weber, "PV-10 might offer the perfect way to prime the immune system." For metasatic melanoma, does PV-10 make ipilimumab (Yervoy), pembrolizumab (MK-3475) and nivolumab relevant?