• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

预防性癌症疫苗引发的人类抗MUC1抗体具有多种效应功能。

Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions.

作者信息

McKeague Michelle L, Lohmueller Jason, Dracz Matthew T, Saadallah Najla, Ricci Eric D, Beckwith Donella M, Ayyalasomayajula Ramya, Cudic Maré, Finn Olivera J

机构信息

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.

出版信息

Antibodies (Basel). 2024 Oct 10;13(4):85. doi: 10.3390/antib13040085.

DOI:10.3390/antib13040085
PMID:39449327
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11503386/
Abstract

BACKGROUND/OBJECTIVES: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection.

METHODS

Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb.

RESULTS

All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC).

CONCLUSIONS

ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.

摘要

背景/目的：粘蛋白-1（MUC1）是一种跨膜糖蛋白，与正常细胞相比，其在癌前和恶性上皮细胞中过度表达且糖基化不足，从而产生了体液免疫和细胞免疫的靶抗原。有晚期结肠腺瘤病史且患结肠癌风险高的健康个体被纳入一项临床试验，以评估使用MUC1肽疫苗预防结肠癌的可行性。使用外周血B细胞和在一年加强免疫后两周收集的血清克隆由该疫苗引发的抗MUC1抗体。对其中12种全人单克隆抗体（mAb）进行了与MUC1+靶细胞结合的测试，并对结合力最强的3种抗体进一步评估了对肿瘤排斥重要的各种效应功能。

方法

在每种mAb存在的情况下，将免疫细胞与表达MUC1表位数量、距离和膜锚定特性不同的靶细胞一起孵育。

结果

所有3种mAb均介导抗体依赖性细胞因子释放（ADCR）、抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）。其中2种还介导抗体依赖性细胞串扰/凋亡（ADCT）。均无补体依赖性细胞毒性（CDC）作用。

结论

当抗体结合靠近膜并锚定在膜上的表位时，ADCP和ADCT功能更有效，这为未来治疗性抗体验证策略提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/f4b3f2ae576d/antibodies-13-00085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/6e5de6db90ea/antibodies-13-00085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/8eafc00ec3a1/antibodies-13-00085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/b09ce560ce9f/antibodies-13-00085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/ac45a8671d67/antibodies-13-00085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/509873609b6a/antibodies-13-00085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/6ef44afbc9ce/antibodies-13-00085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/0aab202a5be8/antibodies-13-00085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/f4b3f2ae576d/antibodies-13-00085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/6e5de6db90ea/antibodies-13-00085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/8eafc00ec3a1/antibodies-13-00085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/b09ce560ce9f/antibodies-13-00085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/ac45a8671d67/antibodies-13-00085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/509873609b6a/antibodies-13-00085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/6ef44afbc9ce/antibodies-13-00085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/0aab202a5be8/antibodies-13-00085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b85/11503386/f4b3f2ae576d/antibodies-13-00085-g008.jpg

相似文献

1
Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions.预防性癌症疫苗引发的人类抗MUC1抗体具有多种效应功能。
Antibodies (Basel). 2024 Oct 10;13(4):85. doi: 10.3390/antib13040085.
2
An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions.一种Fc工程方法，可调节抗体依赖性细胞因子释放而不改变细胞杀伤功能。
MAbs. 2015;7(3):494-504. doi: 10.1080/19420862.2015.1022692.
3
Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine.肿瘤相关黏蛋白 MUC1 的免疫识别是通过一种完全合成的异常糖基化 MUC1 三聚体疫苗实现的。
Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):261-6. doi: 10.1073/pnas.1115166109. Epub 2011 Dec 14.
4
Defucosylation of Tumor-Specific Humanized Anti-MUC1 Monoclonal Antibody Enhances NK Cell-Mediated Anti-Tumor Cell Cytotoxicity.肿瘤特异性人源化抗MUC1单克隆抗体的去岩藻糖基化增强自然杀伤细胞介导的抗肿瘤细胞细胞毒性。
Cancers (Basel). 2021 May 25;13(11):2579. doi: 10.3390/cancers13112579.
5
Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients.乳腺癌患者的MUC1肽疫苗接种可诱导抗体依赖性细胞介导的细胞毒性。
Int J Cancer. 2001 Jul 1;93(1):97-106. doi: 10.1002/ijc.1286.
6
Full-length recombinant antibodies from : production, characterization, effector function (Fc) engineering, and clinical evaluation.全长重组抗体：生产、表征、效应功能（Fc）工程和临床评估。
MAbs. 2022 Jan-Dec;14(1):2111748. doi: 10.1080/19420862.2022.2111748.
7
Detection of circulating anti-MUC1 mucin core protein antibodies in patients with colorectal cancer.结直肠癌患者循环抗MUC1粘蛋白核心蛋白抗体的检测
J Gastroenterol. 1998 Jun;33(3):354-61. doi: 10.1007/s005350050096.
8
Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody.抗MUC-1单克隆抗体DF3及其双特异性抗体介导的乳腺癌细胞吞噬作用
Cancer Res. 2001 May 15;61(10):4061-5.
9
Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity.在乳腺癌细胞表面表达异常糖基化的 MUC1，是抗体依赖的细胞介导的细胞毒性的靶点。
Glycoconj J. 2013 Apr;30(3):227-36. doi: 10.1007/s10719-012-9437-7. Epub 2012 Aug 10.
10
Development of a novel reporter gene assay to evaluate antibody-dependent cellular phagocytosis for anti-CD20 therapeutic antibodies.开发一种新型报告基因检测方法，用于评估抗 CD20 治疗性抗体的抗体依赖性细胞吞噬作用。
Int Immunopharmacol. 2021 Nov;100:108112. doi: 10.1016/j.intimp.2021.108112. Epub 2021 Sep 11.

本文引用的文献

1
Synthesis and Thermodynamic Evaluation of Sialyl-Tn MUC1 Glycopeptides Binding to Macrophage Galactose-Type Lectin.唾液酸化-Tn MUC1 糖肽与巨噬细胞半乳糖型凝集素的结合的合成与热力学评价。
Chembiochem. 2024 Sep 16;25(18):e202400391. doi: 10.1002/cbic.202400391. Epub 2024 Jul 30.
2
Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies.血液恶性肿瘤中嵌合抗原受体 T 细胞耐药的机制。
Nat Rev Drug Discov. 2023 Dec;22(12):976-995. doi: 10.1038/s41573-023-00807-1. Epub 2023 Oct 31.
3
A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity.
CRISPR 激活筛选确定 MUC-21 对于抵抗 NK 和 T 细胞介导的细胞毒性至关重要。
J Exp Clin Cancer Res. 2023 Oct 20;42(1):272. doi: 10.1186/s13046-023-02840-9.
4
Expression of MUC1 in different tumours and its clinical significance (Review).MUC1在不同肿瘤中的表达及其临床意义（综述）
Mol Clin Oncol. 2022 Nov 1;17(6):161. doi: 10.3892/mco.2022.2594. eCollection 2022 Dec.
5
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex.癌细胞通过外核蛋白复合体的激活来抵抗中性粒细胞介导的抗体破坏。
J Immunother Cancer. 2022 Jun;10(6). doi: 10.1136/jitc-2022-004820.
6
Sodium stibogluconate and CD47-SIRPα blockade overcome resistance of anti-CD20-opsonized B cells to neutrophil killing.葡萄糖酸锑钠和 CD47-SIRPα 阻断克服了抗 CD20 调理的 B 细胞对中性粒细胞杀伤的耐药性。
Blood Adv. 2022 Apr 12;6(7):2156-2166. doi: 10.1182/bloodadvances.2021005367.
7
Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis.细胞间 CRISPR 筛选揭示了癌细胞吞噬作用的调控因子。
Nature. 2021 Sep;597(7877):549-554. doi: 10.1038/s41586-021-03879-4. Epub 2021 Sep 8.
8
Mechanisms of Therapeutic Antitumor Monoclonal Antibodies.治疗性抗肿瘤单克隆抗体的作用机制。
Cancer Res. 2021 Sep 15;81(18):4641-4651. doi: 10.1158/0008-5472.CAN-21-1109. Epub 2021 Jun 18.
9
Defucosylation of Tumor-Specific Humanized Anti-MUC1 Monoclonal Antibody Enhances NK Cell-Mediated Anti-Tumor Cell Cytotoxicity.肿瘤特异性人源化抗MUC1单克隆抗体的去岩藻糖基化增强自然杀伤细胞介导的抗肿瘤细胞细胞毒性。
Cancers (Basel). 2021 May 25;13(11):2579. doi: 10.3390/cancers13112579.
10
Calorimetric Analysis of the Interplay between Synthetic Tn Antigen-Presenting MUC1 Glycopeptides and Human Macrophage Galactose-Type Lectin.合成 Tn 抗原呈递 MUC1 糖肽与人巨噬细胞半乳糖型凝集素相互作用的量热分析。
Biochemistry. 2021 Feb 23;60(7):547-558. doi: 10.1021/acs.biochem.0c00942. Epub 2021 Feb 9.