Effect of dose on immune response in patients vaccinated with an HER-2/neu intracellular domain protein-based vaccine
Effect of dose on immune response in patients vaccinated with an HER-2/neu intracellular domain protein-based vaccine
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DOI：
10.1200/jco.2004.09.005
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发表时间：
2004-05-15
影响因子：
45.3
通讯作者：
Cheever, MA
中科院分区：
文献类型：
--
作者：
Disis, ML;Schiffman, K;Cheever, MA
PurposeTo评估HER-2/neu胞内结构域（ICD）蛋白疫苗的安全性，并估计疫苗剂量是否影响immunogeneic.Patients和MethodsTwenty-nine HER-2/neu过度表达乳腺癌或卵巢癌患者，并没有证据表明疾病后，标准治疗接受了低剂量（25杯），中间（150杯），或高剂量（900杯）HER-2/neu ICD蛋白疫苗。疫苗皮内注射，每月一次，共6个月，粒细胞-巨噬细胞集落刺激因子作为佐剂。毒性和细胞和体液HER-2/neu特异性immunity进行了evaluated.ResultsThe疫苗耐受性良好。大多数患者（89%）出现HER-2/neu ICD特异性T细胞免疫。疫苗的剂量并不能预测T细胞反应的程度。大多数患者（82%）还出现HER-2/neu特异性免疫球蛋白G抗体免疫。疫苗剂量不能预测HER-2/neu特异性体液免疫应答的强度或亲和力。然而，高剂量疫苗组与低剂量疫苗组相比，HER-2/neu特异性免疫的出现时间明显更早（P = .003）。超过一半的患者保留HER-2/neu特异性T细胞免疫9至12个月后，免疫接种已经结束. ConclusionHER-2/neu ICD蛋白疫苗是耐受性良好，有效地诱发HER-2/neu特异性T细胞和抗体免疫的大多数乳腺癌和卵巢癌患者谁完成了疫苗方案。虽然疫苗剂量不影响T细胞或抗体免疫的大小，但接受最高剂量的患者比接受最低剂量的患者更快地产生HER-2/neu特异性免疫。(C)2004年，美国临床肿瘤学会。
PurposeTo evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity.Patients and MethodsTwenty-nine patients with HER-2/neu-overexpressing breast or ovarian cancer and with no evidence of disease after standard therapy received a low- (25 mug), intermediate- (150 mug), or high-dose (900 mug) HER-2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly for 6 months, with granulocyte-macrophage colony-stimulating factor as an adjuvant. Toxicity and both cellular and humoral HER-2/neu-specific immunity was evaluated.ResultsThe vaccine was well tolerated. The majority of patients (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did not predict the magnitude of the T-cell response. The majority of patients (82%) also developed HER-2/neu-specific immunoglobulin G antibody immunity. Vaccine dose did not predict magnitude or avidity of the HER-2/neu-specific humoral immune response. Time to development of detectable HER-2/neu-specific immunity, however, was significantly earlier for the high- versus low-dose vaccine group (P = .003). Over half the patients retained HER-2/neu-specific T-cell immunity 9 to 12 months after immunizations had ended.ConclusionThe HER-2/neu ICD protein vaccine was well tolerated and effective in eliciting HER-2/neu-specific T-cell and antibody immunity in the majority of breast and ovarian cancer patients who completed the vaccine regimen. Although the dose of vaccine did not impact the magnitude of T-cell or antibody immunity elicited, patients receiving the highest dose developed HER-2/neu-specific immunity more rapidly than those who received the lowest dose. (C) 2004 by American Society of Clinical Oncology.