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本文引用的文献

1
Pre-clinical safety evaluation of heat shock protein 65-MUC1 peptide fusion protein.热休克蛋白65-MUC1肽融合蛋白的临床前安全性评估。
Regul Toxicol Pharmacol. 2007 Oct;49(1):63-74. doi: 10.1016/j.yrtph.2007.05.005. Epub 2007 May 26.
2
Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835].使用氧化甘露聚糖-MUC1对早期乳腺癌患者进行的III期免疫治疗试点研究[ISRCTN71711835]。
Breast Cancer Res. 2006;8(3):R27. doi: 10.1186/bcr1505. Epub 2006 Jun 15.
3
MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer.晚期胰腺癌或胆管癌患者的MUC1肽疫苗接种。
Anticancer Res. 2005 Sep-Oct;25(5):3575-9.
4
Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers.使用BLP25脂质体疫苗治疗非小细胞肺癌和前列腺癌。
Expert Rev Vaccines. 2005 Jun;4(3):249-57. doi: 10.1586/14760584.4.3.249.
5
Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1).用源自CD227（MUC1）胞质尾的肽疫苗免疫诱导的MUC1转基因小鼠中的肿瘤特异性免疫。
Cancer Immunol Immunother. 2004 Dec;53(12):1068-84. doi: 10.1007/s00262-004-0557-1.
6
Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer.在接受手术切除和局部晚期胰腺癌患者中开展的、使用不同剂量MUC1肽与SB - AS2佐剂组成的MUC1疫苗的I期研究。
Cancer Immunol Immunother. 2005 Mar;54(3):254-64. doi: 10.1007/s00262-004-0581-1. Epub 2004 Sep 14.
7
MUC1 and the MUCs: a family of human mucins with impact in cancer biology.MUC1与黏蛋白家族：对癌症生物学有影响的一类人类黏蛋白
Crit Rev Clin Lab Sci. 2004;41(2):189-231. doi: 10.1080/10408360490452040.
8
Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer.采用表达人MUC1的改良痘苗病毒（MVA）进行I期免疫治疗，作为MUC1阳性晚期癌症患者的抗原特异性免疫治疗。
J Gene Med. 2003 Aug;5(8):690-9. doi: 10.1002/jgm.397.
9
Development and preclinical evaluation of a Bacillus Calmette-Guérin-MUC1-based novel breast cancer vaccine.一种基于卡介苗-粘蛋白1的新型乳腺癌疫苗的研发及临床前评估。
Cancer Res. 2003 Mar 15;63(6):1280-7.
10
MUC1 and the immunobiology of cancer.黏蛋白1与癌症免疫生物学
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用两种重组卡介苗疫苗进行免疫接种，这两种疫苗结合了粘蛋白-1多个串联重复序列的表达和集落刺激因子，可抑制小鼠乳腺肿瘤生长。

Immunization with two recombinant Bacillus Calmette-Guérin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice.

作者信息

Yuan Shifang, Shi Changhong, Ling Rui, Wang Ting, Wang Hui, Han Wei

机构信息

Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Xi'an, 710033, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2010 Sep;136(9):1359-67. doi: 10.1007/s00432-010-0787-x. Epub 2010 Feb 3.

DOI:10.1007/s00432-010-0787-x
PMID:20127358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11827772/
Abstract

PURPOSE

Mucin-1 (MUC1) is a breast tumor-associated antigen. However, clinical trials with MUC1 showed that, with respect to its expression levels, MUC1 is a relatively poor immunogen in human beings. Evidence showed that MUC1-specific immunodominant B and T cell epitopes are derived from the variable-number tandem repeat (VNTR) region. Therefore, immunotherapy that targets multiple VNTRs may induce anti-MUC1 immune responses. GM-CSF has been shown to increase the percentage and activity of antigen-presenting cells. In this study, we constructed two recombinant Bacillus Calmette-Guérin (BCG) vaccines that combine the expression of multiple tandem repeats of MUC1 and CSF. The effect of two novel breast cancer vaccines (rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF) on the growth of breast tumor on hu-PBL-SCID mice was evaluated.

METHODS

We coupled VNTRs (4 and 8) of MUC1 with GM-CSF (MVNTR4-CSF and MVNTR8-CSF). The MVNTR4-CSF and MVNTR8-CSF were inserted into the pDE22 plasmid and transformed into competent BCG by electroporation. The effect of both BCG vaccines on the growth of breast tumor on hu-PBL-SCID mice was evaluated.

RESULTS

The growth of MUC1-positive breast tumors from hu-PBL-SCID mice immunized with two vaccines was significantly inhibited.

CONCLUSIONS

rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines may be good candidates for breast tumor immunotherapy.

摘要

目的

黏蛋白1（MUC1）是一种乳腺肿瘤相关抗原。然而，针对MUC1的临床试验表明，就其表达水平而言，MUC1在人类中是一种相对较弱的免疫原。有证据表明，MUC1特异性免疫显性B细胞和T细胞表位源自可变数目串联重复序列（VNTR）区域。因此，靶向多个VNTR的免疫疗法可能诱导抗MUC1免疫反应。已证明粒细胞-巨噬细胞集落刺激因子（GM-CSF）可增加抗原呈递细胞的百分比和活性。在本研究中，我们构建了两种重组卡介苗（BCG）疫苗，它们结合了MUC1多个串联重复序列和GM-CSF的表达。评估了两种新型乳腺癌疫苗（rBCG-MVNTR4-CSF和rBCG-MVNTR8-CSF）对人外周血淋巴细胞-严重联合免疫缺陷（hu-PBL-SCID）小鼠乳腺肿瘤生长的影响。

方法

我们将MUC1的VNTR（4和8）与GM-CSF（MVNTR4-CSF和MVNTR8-CSF）偶联。将MVNTR4-CSF和MVNTR8-CSF插入pDE22质粒，并通过电穿孔转化到感受态卡介苗中。评估了两种卡介苗对hu-PBL-SCID小鼠乳腺肿瘤生长的影响。

结果

用这两种疫苗免疫的hu-PBL-SCID小鼠的MUC1阳性乳腺肿瘤生长受到显著抑制。

结论

rBCG-MVNTR4-CSF和rBCG-MVNTR8-CSF疫苗可能是乳腺肿瘤免疫治疗的良好候选疫苗。