Toxicity, Immunogenicity, and Induction of E75-specific Tumor-lytic CTLs by HER-2 Peptide E75 (369–377) Combined with Granulocyte Macrophage Colony-stimulating Factor in HLA-A2+ Patients with Metastatic Breast and Ovarian Cancer

摘要: To determine the toxicity and immunogenicity of HER-2/neu, HLA-A2-restricted peptide E75 in patients with metastatic breast ovarian cancer, 14 were vaccinated escalating amounts (100, 500, 1000 microg) mixed 250 microg granulocyte macrophage colony-stimulating factor as adjuvant. Each vaccine dose was administered a total volume 1.5 ml divided into four intradermal injections weekly for 4 weeks, followed by monthly boosts 10 injections. Vaccinations well tolerated without significant toxicity. Blood drawn before, at 8 up to 13-16 months after vaccination measurement cellular immunity. Seven tested had delayed type hypersensitivity defined >5 mm induration. Peripheral blood mononuclear cells from 5 9 proliferated stimulation index > or = 2.0. Of induction CTL response, responded autologous dendritic plus cytokines eliciting E75-specific lytic activity consistent presence activated/memory cells, 2 others vitro + interleukin-12 +/- anti-CD152(33KD), whereas did not respond. Four CTLs present specifically recognized on indicator tumors demonstrated cold-target inhibition tumor lysis. These showed IFN-gamma production. peripheral cell 3 these E75, but indices higher prevaccine samples. All DTH responses E75. results demonstrate that E75+ can induce both peptide-specific epitope specific CTLs, which lyse HER-2/neu+ stage IV patients.