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.
Highlights
Intralesional (IL) injection of anti-tumor therapeutic agents has been used for the treatment of cutaneous malignancies
Bacillus CalmetteGuerin (BCG) is the most extensively studied of these agents
Intralesional BCG has been associated with patient fatalities due to anaphylactic hypersensitivity reactions that have not been reported with PV-10 [20,21,22,23,24]
Summary
Intralesional (IL) injection of anti-tumor therapeutic agents has been used for the treatment of cutaneous malignancies. IL therapy can control local disease and avoid potential surgical complications and systemic toxicity While many of these agents lead to regression of injected lesions, systemic responses are rarely observed limiting this strategy for patients with metastatic disease. Intratumoral injection of dendritic cells (DCs) has led to increased lymphocyte infiltration and systemic anti-tumor effects in patients with advanced melanoma [1,2]. Injection of adjuvants such as BCG or TLR agonists has been shown to enhance tumor-specific immunity [3,4,5,6]. Intratumoral injection of immune-enhancing cytokines such as IL-2 or GM-CSF has been shown to enhance anti-tumor immunity in melanoma patients. [6,7]
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