Use of Booster Inoculations to Sustain the Clinical Effect of an Adjuvant Breast Cancer Vaccine From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Use of Booster Inoculations to Sustain the Clinical Effect of an Adjuvant Breast Cancer Vaccine From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
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DOI：
10.1002/cncr.25586
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发表时间：
2011-02-01
期刊：
影响因子：
6.2
通讯作者：
Peoples, George E.
中科院分区：
文献类型：
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作者：
Holmes, Jarrod P.;Clifton, Guy T.;Peoples, George E.
背景：作者正在临床无病乳腺癌 (BC) 患者中进行 HER-2/neu E75 肽疫苗的临床试验。他们的 1-2 期试验表明，E75 + 粒细胞巨噬细胞集落刺激因子 (GM-CSF) 疫苗在刺激 E75 特异性 CD8(+) T 细胞的克隆扩增方面是安全有效的。他们评估了初级疫苗接种系列完成后对加强疫苗的需求和反应。方法：参加 E75 疫苗试验的 BC 患者在完成初级疫苗接种系列后 6 个月以上，接受 E75 + GM-CSF 加强接种。监测患者的毒性。在加强免疫前后，使用人白细胞抗原-A2：免疫球蛋白G二聚体对E75特异性CD8(+) T细胞进行定量。结果：53 名患者接受了疫苗加强接种。初次疫苗接种系列的中位时间为 9 个月（范围，6-35 个月），中位残留 E75 特异性免疫力为 0.70%（范围，0-3.49%）CD8(+) 淋巴细胞。初次疫苗接种系列后 6 个月时，94.4% 的患者出现残余免疫力 (ERI) 升高（CD8(+) E75 特异性 T 细胞 >0.5%），而在 > 6 个月时，这一比例为 48% (P = .002)。加强剂耐受性良好，仅观察到 1 级和 2 级毒性。与 6 个月以上的患者相比，初次接种系列后 6 个月时接受加强疫苗的患者的局部反应更为强烈（99.4 +/- 6.1 mm vs 81.8 +/- 4.1 mm，P = .01）。在缺乏 ERI 的患者中，85% 的患者在接种疫苗后 ERI 增加 (P = .0014)。结论：HER-2/neu E75 肽疫苗 E75 可刺激无病 BC 患者的特异性免疫力。然而，免疫力会随着时间的推移而减弱。对于没有 ERI 的患者，疫苗加强剂可以安全有效地刺激 E75 特异性免疫力。这些结果表明，在完成初级疫苗接种系列后 6 个月时，加强疫苗可能最有效。癌症 2011；117：463-71。美国癌症协会 2010 年出版。*
BACKGROUND: The authors are conducting clinical trials of the HER-2/neu E75-peptide vaccine in clinically disease-free breast cancer (BC) patients. Their phase 1-2 trials revealed that the E75 + granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8(+) T cells. They assessed the need for and response to a booster after completion of primary vaccination series. METHODS: BC patients enrolled in the E75 vaccine trials who were >= 6 months from completion of their primary vaccination series were offered boosters with E75 + GM-CSF. Patients were monitored for toxicity. E75-specific CD8(+) T cells were quantified using the human leukocyte antigen-A2: immunoglobulin G dimer before and after boosting. RESULTS: Fifty-three patients received the vaccine booster. Median time from primary vaccination series was 9 months (range, 6-35 months), and median residual E75-specific immunity was 0.70% (range, 0-3.49%) CD8(+) lymphocytes. Elevated residual immunity (ERI) (CD8(+) E75-specific T cells >0.5%) was seen in 94.4% of patients at 6 months from primary vaccination series versus 48% of patients at >6 months (P = .002). The booster was well tolerated, with only grade 1 and 2 toxicity observed. Local reactions were more robust in patients receiving the booster at 6 months from primary vaccination series compared with those at >6 months (99.4 +/- 6.1 mm vs 81.8 +/- 4.1 mm, P = .01). In patients lacking ERI, 85% had increased ERI after vaccination (P = .0014). CONCLUSIONS: The HER-2/neu E75 peptide vaccine E75 stimulates specific immunity in disease-free BC patients. However, immunity wanes with time. A vaccine booster is safe and effective in stimulating E75-specific immunity in those patients without ERI. These results suggest that the booster may be most effective at 6 months after completion of the primary vaccination series. Cancer 2011;117:463-71. Published 2010 by the American Cancer Society.*