A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.

摘要: Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance mice. We hypothesized that cyclophosphamide-modulated vaccination mAb safely induces relevant immunity HER2+ Adding both cyclophosphamide the 7.16.4 to maximized CD8+ T-cell tumor-free survival transgenic We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic GM-CSF-secreting vaccine, weekly trastuzumab 20 Primary clinical trial objectives were safety benefit, which benefit represents complete response + partial stable disease. Secondary assess responses delayed type hypersensitivity (DTH) intracellular cytokine staining. Patients received three monthly vaccinations, boost 6 8 months from entry. This combination immunotherapy was safe, rates at 1 year 55% [95% confidence interval (CI), 32%-77%; P = 0.013] 40% (95% CI, 19%-64%), respectively. Median progression-free overall durations 7 4-16) 42 22-70), Increased DTH developed [of whom 4 had 18-90)], trend toward longer responders. Polyfunctional T cells progressively expanded across cycles. Further investigation is warranted.