Intralesional Injection of Rose Bengal Induces a Systemic Tumor-Specific Immune Response in Murine Models of Melanoma and Breast Cancer |
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Authors: | Paul Toomey Krithika Kodumudi Amy Weber Lisa Kuhn Ellen Moore Amod A Sarnaik Shari Pilon-Thomas |
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Institution: | 1. H. Lee Moffitt Cancer Center and Research Institute, Immunology Program, Tampa, Florida, United States of America.; 2. H. Lee Moffitt Cancer Center and Research Institute, Cutaneous Oncology Program, Tampa, Floria, United States of America.; 3. University of South Florida, College of Medicine, Tampa, Florida, United States of America.; 4. University of South Florida, Department of Oncologic Sciences, Tampa, Florida, United States of America.; Istituto Superiore di Sanità, Italy, |
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Abstract: | Intralesional (IL) injection of PV-10 has shown to induce regression of both injected and non-injected lesions in patients with melanoma. To determine an underlying immune mechanism, the murine B16 melanoma model and the MT-901 breast cancer model were utilized. In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions. In a murine model of melanoma, B16 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL PV-10 led to regression of the injected lesion as well as the distant B16 melanoma lung metastases. Anti-tumor immune responses were measured in splenocytes collected from mice treated with IL PBS or PV-10. Splenocytes isolated from tumor bearing mice treated with IL PV-10 demonstrated enhanced tumor-specific IFN-gamma production compared to splenocytes from PBS-treated mice in both models. In addition, a significant increase in lysis of B16 cells by T cells isolated after PV-10 treatment was observed. Transfer of T cells isolated from tumor-bearing mice treated with IL PV-10 led to tumor regression in mice bearing B16 melanoma. These studies establish that IL PV-10 therapy induces tumor-specific T cell-mediated immunity in multiple histologic subtypes and support the concept of combining IL PV10 with immunotherapy for advanced malignancies. |
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