Intralesional Injection of Rose Bengal Induces an Anti-tumor Immune Response and Potent Tumor Regressions in a Murine Model of Colon Cancer

An abstract from the March 2015 Society of Surgical Oncology 68th Annual Cancer Symposium by Pardiwala et al., University of Illinois at Chicago (P134, see page S86):

INTRODUCTION: Early phase studies using intratumoral injection of PV-10 (10% Rose Bengal) have shown regression of in-transit melanoma deposits and non-treated bystander lesions. The effects of PV-10 on colorectal cancer (CRC) cells and established tumors is unknown. METHODS: Murine and human colorectal cancer cells were treated in vitro with varying concentrations of PV-10. Cell viability was determined by the MTS assay, trypan blue, DAF-FM, and SNARF-1 staining. To determine an underlying immune mechanism, a murine CT26 syngeneic CRC model was utilized. Bilateral subcutaneous CRC cell tumors were established in Balb/C mice and one tumor in each mouse was injected with PV-10 at a dose equal to half the calculated tumor volume. Tumors were measured daily. Splenocytes from treated animals were co-cultured with irradiated CT26 cells and supernatants analyzed for INF-γ production by ELISA. RESULTS: PV-10 induced near total cell death, corresponding increases in nitric oxide production, and decreased intracellular pH in both CT26 murine and HT29 human CRC cells within hours of exposure compared to controls (p<0.01), and at levels similar to 5FU. Treatment of subcutaneous tumors with a single injection of intralesional PV-10 led to near complete responses in all animals within days of exposure and significant regression of the injected lesions compared to controls (n=6 per group, p=0.027). PV-10 treatment was associated with occasional bystander responses in contralateral untreated tumors and trended towards a decreased rate of growth in these lesions. Splenocytes isolated from tumor bearing mice treated with PV-10 displayed enhanced tumor-specific IFN-γ production compared to splenocytes from PBS-treated mice (p = 0.025). CONCLUSION: Rose Bengal induced potent cell death in human and murine colon cancer cells in vitro. Intralesional injection in established tumors induced an anti-tumor immune response and significant tumor regressions in vivo. These studies establish that intralesional PV-10 therapy warrants further study as a potential immunotherapeutic agent in colorectal cancer and metastases.

Click to enlarge.

$PVCT: Waiting for MoffittCancerCenter (@MoffittNews)

I previously wrote that: I asked Pete for his perspective on it in the context of management's work with the FDA. Regulatory approval is a complex topic, especially as it relates to local agent PV-10 versus systemic ones. PV-10 as a local agent is a reality that has driven management's MM Phase 3 trial design more than anything else. The key to the FDA, according to Peter, is proving "clinical relevance." This certainly means meeting endpoints, but it also means whether a drug should be approved or not. PV-10 needs to be clinically relevant to be approved. Provectus' Phase 3 trial design discussed with the FDA would support PV-10 as being "clinically relevant."

With two days left, the blog's poll -- What company achievement will have the greatest impact on share price in Q1? -- has 13% of participants voting for Moffitt's data. I previously wrote that I don't think Moffitt's full effect will be felt this quarter. That does not mean I think Moffitt is not important. It appears Moffitt is crucial to Provectus, PV-10 and Rose Bengals' story.

Management will not say where, when and what Moffitt will say about the cancer center's follow-up mouse work to SSO (recall here and here), and whether some of Moffitt's human trial work results will be available concurrently with the mouse work.

So, we wait...

Peter says "Everyone, and I mean everyone, wants to better understand the systemic benefit of PV-10." With that, I assume "everyone" includes the FDA. Management's silence on Moffitt's results as well as the timing and venues of their presentation and publication suggest to me the FDA, Big Pharma and serious life sciences investors also have not seen Moffitt's full data-set.

In Provectus' CEO Letter last April, management discussed how Moffitt's work was "...fundamental for full characterization of PV-10's systemic benefit and may provide pivotal support for accelerated approval in the U.S." Accelerated approval is a real possibility, given the basis for seeking such is the import of Moffitt's work.

Moffitt weighing in on PV-10's clinical relevance and the timing of these comments should give us great insight into whether and when the management might state it is appropriate to seek accelerated approval based on discussions with the FDA.