|Click to enlarge. Original image source (Google search of "immunotherapy").|
Colored editing above is mine.
- First, PV-10 (Rose Bengal) ablates all solid tumors (UIC: "We have previously demonstrated that human and murine colon cancer cells undergo near complete cell death in vitro and in vivo upon direct exposure to PV-10, a synthetic dye currently in clinical trails for intralesional therapy of in-transit melanoma", and
- Second, PV-10 primes the immune system in all solid tumors (UIC: "Therefore, based on these results, further evaluation of PV-10 as a potential agent to stimulate immunologic cell death in solid tumors is warranted.").
Said differently, and perhaps with the benefit of more clinical data, particularly that from Provectus' Phase 1b/2 study PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma, PV-10 should be called an immunotherapy. This small molecule that generates clinical benefit for and positive outcomes in cancer patients from its physical chemistry has feelings too.
Moffitt Cancer Center in its SITC 2015 poster entitled Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity via High Mobility Group Box 1, noted:
"IL RB therapy also increased antigen-specific T cell proliferation and enhanced tumor regression. In addition, IL RB facilitated dendritic cells (DCs) infiltrating lymph nodes draining from tumor. Incubation of melanoma cells with RB led to necrosis and the release of High Mobility Group Box 1 (HMGB1), which activated DCs. The blockade of HMGB1 significantly reduced the antigen-presenting ability of DCs."
UIC noted in their ASC 2016 abstract:
"Treatment of colon cancer cells with PV-10 induced cell cycle arrest, apoptosis, autophagy, and significant ER stress; consistent with immunogenic apoptosis. In order for cytotoxic agents to act as potential immunotherapeutic strategies in the treatment of solid tumors, immunogenic cell death targeting the endoplasmic reticulum (ER), leading to ER stress may be critical."
Underlined emphasis above and below is mine.
Playing scientist using Google, note for example abstract comments from Zhu et al. in Endoplasmic reticulum stress and its regulator XBP-1 contributes to dendritic cell maturation and activation induced by high mobility group box-1 protein (Int J Biochem Cell Biol. 2012 Jul;44(7):1097-105):
"High mobility group box-1 protein (HMGB1) had been proved to induce maturation and activation of dendritic cell (DC), however, the endogenous changes and mechanisms underlying are unknown. Since endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular survival and repair, we hypothesized that HMGB1 may regulate the function of DC by modulating ERS. In our study, HMGB1 stimulation induced significant ERS responses in DCs in a time- and dose-dependent manner, demonstrated by the up-regulation of a number of ERS markers."
Note: CGMP = Current Good Manufacturing Practice (CGMP). See for example Drug Applications and Current Good Manufacturing Practice (CGMP) Regulations.