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[摘要]：The promise of cancer vaccines remains as yet unrealized as a reliable and effective therapeutic modality. There is now compelling evidence that collateral induction of antitumor immune responses contributes substantially to viral antitumor activities. In addition to the expected antiviral immune clearance, the "danger" signal created by virus-infected cells can generate immune costimulation known to override immune suppression and reverse tolerance within the tumor microenvironment. OncoVEX(GM-CSF) (JS1/34.5(-)/47(-)/GM-CSF) is a gene-modified, immune-enhanced oncolytic herpes simplex virus type 1 (HSV-1) with preclinical confirmation of mode of action and phase I and II evidence of safety when administered as an intratumoral in situ vaccination. A phase II study in 50 patients with stage IIIC and IV melanoma showed a 28% response rate, including 70 complete responses, with demonstrable durability of effect. This included patients who continued on a compassionate dosing extension study. Immune response analyses of tumor-infiltrating lymphocytes and peripheral blood mononuclear cells confirmed that in situ vaccination elicits both local and systemic antitumor-specific immune responses, establishing proof of principle for this therapeutic approach in the clinical setting. A pivotal randomized phase Ill study of OncoVEX(GM-CSF) in melanoma has been initiated and will provide additional data. |
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