June 5, 2015

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.
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