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负载HER-2/neu多肽的树突状细胞激发特异性CTL反应

孟东 时伟锋 孙春雷 时宏珍 史央 朱晨瑶 唐金海

中国肿瘤生物治疗杂志2012,Vol.19Issue(1):29-34,6.
中国肿瘤生物治疗杂志2012,Vol.19Issue(1):29-34,6.DOI:10.3872/j.issn.1007-385X.2012.01.005

负载HER-2/neu多肽的树突状细胞激发特异性CTL反应

Specific CTL response induced by dendritic cells pulsed with HER-2/neu peptide

孟东 1时伟锋 1孙春雷 1时宏珍 2史央 2朱晨瑶 2唐金海3

作者信息

  • 1. 苏州大学附属第四医院乳腺外科,江苏无锡,214035
  • 2. 南京市免疫细胞工程技术研究中心,南京得康生物技术有限公司,江苏南京,210019
  • 3. 江苏省肿瘤医院普通外科,江苏南京,210000
  • 折叠

摘要

Abstract

Objective; To explore the potential of autologous dendritic cells (DCs) pulsed with HER-2/neu peptide in inducing specific cytotoxic T lymphocyte (CTL) response and feasibility of breast cancer vaccines. Methods; Seventeen breast cancer patients with positive HLA-A201 and HER-2/neu were enrolled and their peripheral blood mononuclear cells and lymphocytes were isolated and induced into DCs and pulsed with HER-2/neu peptide. The killing effect of CTLs against T2 cell line pulsed with HLA-A201 -binding peptide HER-2/neu was determined. The patients were inoculated subcutaneously near the inguinal region with auto-DCs pulsed with HER-2/neu peptide for 4 times every week. The immu-nological responses and clinical responses were examined in 1 week after the final vaccination. Results; The average percentage of special CTLs primed by DCs pulsed with HER-2/neu peptide was significantly higher than that in the control group (CTLs primed by DCs unloaded with HER-2/neu peptide) ( [5.41 ± 1.44]% ts [0. 41 ±0. 12] % , P <0. 05 ).CTLs induced by DCs exerted a stronger killing effect on T2 cell line pulsed with HER-2/neu peptide than that in control group ([35.5±4.7]% vs [11.2 ±1.4]% at the ratio of E [effect] to T [target] as 30: 1 ,P <0.05). Vaccination of DCs was well tolerated and no toxicity was observed. The cytokine levels in sera such as IL-2, IL-12 and IFN--y were increased after vaccinations ([148.79 ±28.32] ng/ml vs [409.09 ±89. 39] ng/ml, [24.49 ±56.23] ng/ml vs [56.23± 14.08] ng/ml, [67.77 ±39.35] ng/ml vs [ 146.57 ±25.97] ng/ml, respectively, allP<0.05). The cytokine levels in sera such as TNF-a and IL-10 had no significant changes before and after vaccination. The results of DTH test were positive in 8 patients (8/17) , and the percentages of antigen-specific IFN-7* CD8 + T increased in 8 patients (8/17). Conclusion: Auto-DC vaccines pulsed with HER-2/neu peptide can elicit specific immune responses ex vivo and in vivo, and induce secretion of Thl type cytokines from DCs and have no adverse reaction.

关键词

树突状细胞/乳腺癌/HER-2/neu多肽/细胞毒性T淋巴细胞/免疫治疗

Key words

dendritic cell/ breast cancer/ HER-2/neu peptide/ cytotoxic T lymphocyte/ immunotherapy

分类

医药卫生

引用本文复制引用

孟东,时伟锋,孙春雷,时宏珍,史央,朱晨瑶,唐金海..负载HER-2/neu多肽的树突状细胞激发特异性CTL反应[J].中国肿瘤生物治疗杂志,2012,19(1):29-34,6.

基金项目

南京市科学技术委员会高新技术产业化项目资助(No.201103058). (No.201103058)

中国肿瘤生物治疗杂志

OA北大核心CSCDCSTPCD

1007-385X

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