September 25, 2015

provectus IS a t-cell company

H/t InvestorVillage poster bradpalm1: A research team from the University of Illinois at Chicago (UIC) published a paper in July entitled The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses (Maker et al., J Clin Cell Immunol 2015, 6:4). This same team previously published results of their murine model work and research on PV-10 for colon cancer. See June 5, 2015 blog post Intralesional Injection of Rose Bengal Induces an Anti-tumor Immune Response and Potent Tumor Regressions in a Murine Model of Colon Cancer.

Blog post takeaways:
  • Rose Bengal (PV-10)/PV-10 (Rose Bengal) induces/generates/creates/leads to anti-tumor immunity. To some the so-called Holy Grail of cancer therapy is achieving durable [system- or body-wide] anti-tumor immunity in a cancer patient.
  • PV-10 can prime the immune system (through the direction injection of the compound into cancerous lesions), and help it defeat distant cancerous lesions around the body.
  • The compound exposes antigens to the immune system that otherwise would not be exposed, or that otherwise would escape detection by (and thus presentation to) the immune system.
  • PV-10 can help with T cell generation & circulation, even after treatment with immune checkpoint inhibitors fails.
  • UIC's work reproduced Moffitt Cancer Center's (Moffitt's) work, which reproduced Provectus' founders' work.
Recall that Provectus has a two-prong approach to fighting (killing) cancer: (i) local effect/tumor ablation (anti-tumor cytotoxicity) and (ii) systemic effect/tumor-specific immune response (induction of anti-tumor immunity)
Click to enlarge. Image source
UIC and Moffitt independently reproduced the veracity of both prongs:
Click to enlarge. Image source
UIC's paper reviews PV-10's agnosticity in destroying tumors into which it is injected (i.e., anti-tumor cytotoxicity):
  • Melanoma,
  • Breast cancer,
  • Ovarian cancer,
  • Gastric cancer, and
  • Sarcoma.
The paper discusses PV-10's agnosticity in generating anti-tumor immunity resulting from local tumor injection (i.e., from resultant anti-tumor cytotoxicity):
  • Melanoma,
  • Breast cancer, and
  • Hepatocellular carcinoma (HCC).
The UIC team appears to have conducted murine model work on PV-10 in HCC, noting "Our current research is establishing the role of RB in generating anti-tumor immune responses in gastrointestinal cancer and liver metastases:"
"Furthermore, in syngeneic orthotopic models of murine hepatocellular carcinoma (HCC), RB similarly induced chemoablation in all treated tumors. Twenty-one to 81 days after RB treatment, when re-challenged with the same tumor, durable immunity was demonstrated in 14/14 animals without measurable tumor formation, whereas B16-F10 melanoma tumors, i.e., non-HCC cells, were able to be established in 13/13 animals [20]. Additionally, immunity to establishment of a new HCC tumor could be created through adoptive transfer of splenocytes from treated animals. This was an interesting finding given that analysis of splenic composition from animals with B16 melanoma that experienced distant lung tumor regression after RB treatment of flank tumors did not demonstrate any difference in the percent of T cells, Tregs, NK cells, B cells, myeloid derived suppressor cells, or macrophages [15]. The authors further demonstrated that bystander lesions disappeared or decreased in size in HCC models, whereas, no bystander tumors were ever observed to resolve in nude mice without a competent T-cell immune system. These experiments established that, similar to melanoma, in immunocompetent mice with orthotopic primary hepatocellular carcinoma flank tumors, an anti-tumor response can be induced by priming the animals with RB treatment of tumors. These experiments raise the possibility that RB induced cytotoxicity exposes antigens and mounts an immune response that may protects animals from additional tumor formation that can be adoptively transferred to other animals using splenocytes." {Underlined and bolded emphasis is mine}
Speaking of antigens, it's all about the antigens:
"These experiments established that in human and murine melanoma and breast cancer, there appeared to be an antigen-driven T-cell response that has the potential to activate T-cells and impart antitumor responses in bystander lesions and distant metastases."
Why are antigens important? Because they facilitate the priming of the immune system through their presentation to it:
"These findings may imply that tumor response in the primary lesion may be able to prime the immune system of patients for activity against distant lesions."
The UIC team's conclusions could be profound, among them:
  • "RB-mediated tumor cell death may expose tumor antigens that may otherwise evade immune detection."
  • "Though most profoundly described in melanoma cells, clearly an immunoreactive malignancy, the effect has been shown to be not limited to one specific type of malignancy. 
  • "Decrease in tumor burden and stimulation of an immune response with PV-10 has been demonstrated in animal models of metastasis, and correlations of these responses in clinical studies is consistent with such results." Provectus' CTO Dr. Eric Wachter, PhD has said in a 2013 white paper: "PV-10 murine research demonstrated unambiguously, Dr. Wachter noted, that tumor burden is a critical variable in predicting response to a combination therapy." See Radiation (September 22, 2015) on the blog's Current News page.
  • "That PV-10 treatment can potentially increase circulating cytotoxic T-cells, even in patients who were previously treated with immune-activating checkpoint blockade, supports the possibility that RB induced cytotoxicity may activate T-cells that are responsible for the bystander effect on untreated lesions."
  • As such, intralesional therapy with RB may be a promising new mode of therapy to stimulate T-cell mediated anti-tumor immune responses."
UIC's work was conducted in part under an NIH grant.

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