Provectus Presents Nonclinical Data on Antitumor Immune Response to PV-10 Immuno-Chemoablation
Monday October 29, 2012
-- Additional Data Demonstrates Use Of PV-10 in Combination with Systemic Chemotherapy --
-- Data Presented at Society for Immunotherapy of Cancer 27th Annual Meeting --
Provectus presented nonclinical data on PV-10 at the Society for Immunotherapy of Cancer (SITC) 27th Annual Meeting on October 26 and 27, 2012 in North Bethesda, MD. PV-10 is Provectus Pharmaceuticals's novel oncology drug designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects.
The data were presented in Poster Presentation #135, Abstract #1452582, entitled "Generation of an antitumor response and immunity using a small molecule drug (PV-10)." The poster was presented by Dr. Craig Dees, PhD, CEO and Savannah Blair of Provectus and authored by Dr. Dees along with co-authors S. Blair, J. Harkins, T.C. Scott and E.A. Wachter. A copy of the poster can be found at the following link: http://www.pvct.com/publications/SITC-Poster-23Oct12.pdf
The mechanism by which PV-10's bystander effect is produced was investigated using hepatocellular carcinoma (HCC) and melanoma tumors in immunocompetent and immunodeficient mice. In one set of experiments using immunocompetent mice with bilateral HCC tumors (i.e., two HCC tumors in opposite flanks), intralesional injection of PV-10 into one of the two tumors led not only to eradication of the injected tumor, but also to regression of the uninjected tumor. Controls treated with saline exhibited no effect in either tumor. Treatment of mice with systemic chemotherapy (i.e., 5-fluorouracil, "5-FU") had minimal effect on either tumor, while combination of intralesional PV-10 with systemic 5-FU elicited maximal response in uninjected tumors. Data were analyzed by tumor (i.e., injected tumor, uninjected tumor and total tumor burden) for time to progression and for tumor growth. PV-10 alone was favorable to saline control in all categories, while PV-10 combination therapy produced highly significant advantage vs. control for time to progression of treated tumors (p = 0.010), untreated tumors (p = 0.011) and total tumor burden (p = 0.004).
The immunologic response following PV-10 treatment was also investigated in experiments using melanoma tumors synchronously induced in the flank and lungs of immunocompetent mice. Ablation of the flank tumor with PV-10 led to a dramatic reduction of lung metastases (mean of 4 metastases per animal) vs. control (mean of more than 81 metastases). This outcome is similar to that reported in March 2012 by Toomey et al. at the Society of Surgical Oncology (SSO) annual meeting, confirming the biological relevance of PV-10 immuno-chemoablation. A copy of Dr. Toomey's poster from SSO can be found at the following link: http://www.pvct.com/publications/Paul-Toomey-PV10-SSO-2012.pdf
Rechallenge data were also presented demonstrating that ablation of HCC tumors in immunocompetent mice induced tumor specific immunity. In particular, mice that had undergone ablation of their HCC tumors rejected attempted reimplantation with HCC tumor cells (i.e., rechallenge), but had no response against melanoma cells. In contrast, immunodeficient mice exhibited no resistance upon rechallenge with HCC tumor cells following ablation of their HCC tumor. Resistance against the ablated tumor cell line was shown to be transferable via adoptive transfer of spleen cells from PV-10 treated donor mice to naive mice. Control animals receiving spleen cells from untreated donor mice exhibited no immunity to implantation with the tumor cell line.
Posted: October 2012