黏蛋白在肿瘤免疫治疗中的研究进展

doi:10.19586/j.2095-2341.2023.0017

生物技术进展 ›› 2023, Vol. 13 ›› Issue (3): 390-398.DOI: 10.19586/j.2095-2341.2023.0017

黏蛋白在肿瘤免疫治疗中的研究进展

高朗(), 于思雪, 袁春森, 单志伟, 赵鹏翔()

北京工业大学环境与生命学部，北京 100124

收稿日期:2023-02-17 接受日期:2023-03-21 出版日期:2023-05-25 发布日期:2023-06-12
通讯作者: 赵鹏翔
作者简介:高朗 E-mail: 15611140435@163.com；
基金资助:
北京市科技新星计划交叉合作课题项目(20220484218)

Research Progress of Mucin in Tumor Immunotherapy

Lang GAO(), Sixue YU, Chunsen YUAN, Zhiwei SHAN, Pengxiang ZHAO()

Faculty of Environment and Life，Beijing University of Technology，Beijing 100124，China

Received:2023-02-17 Accepted:2023-03-21 Online:2023-05-25 Published:2023-06-12
Contact: Pengxiang ZHAO

摘要/Abstract

摘要：

黏蛋白是一类主要由黏多糖组成的高分子量糖蛋白，其主要分布在人体的各种管腔内表面，对上皮细胞起到保护和润滑作用。多项研究表明，黏蛋白在肿瘤的发生发展中扮演着重要角色，因此，部分黏蛋白被确定为肿瘤标志物，成为很有前景的肿瘤治疗靶点。综述了目前以黏蛋白为靶点的肿瘤治疗方案，包括小分子抑制剂、抗体疗法、疫苗等方面，以期为临床肿瘤诊治方法的发展与优化提供理论参考。

关键词: 黏蛋白, 肿瘤, 免疫疗法, 疫苗

Abstract:

The mucin （MUC） family is a group of highly glycosylated macromolecules，which is mainly distributed in the body of various lumen surface， playing a role in protecting and lubricating epithelial cells. Many studies have shown that mucins play an important role in the occurrence and development of tumors. Therefore， some mucins have been identified as tumor markers and become promising tumor therapeutic targets. This paper reviewed the current mucin-targeted tumor therapy， including small molecule inhibitors， antibody therapy， vaccines， etc， hoping to provide theoretical reference for the development and optimization of clinical tumor diagnosis and treatment methods.

Key words: mucin, tumour, immunotherapy, vaccine

中图分类号:

R730.51

高朗, 于思雪, 袁春森, 单志伟, 赵鹏翔. 黏蛋白在肿瘤免疫治疗中的研究进展[J]. 生物技术进展, 2023, 13(3): 390-398.

Lang GAO, Sixue YU, Chunsen YUAN, Zhiwei SHAN, Pengxiang ZHAO. Research Progress of Mucin in Tumor Immunotherapy[J]. Current Biotechnology, 2023, 13(3): 390-398.

图/表 4

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抑制剂种类	药物名称	肿瘤类型	研究现状	参考文献
多肽	GO-203	人十二指肠腺癌	临床前研究	[10]
		食管鳞状细胞癌	临床前研究	[11, 16]
		尿路上皮癌	临床前研究	[12]
		急性髓系白血病	临床前研究	[17-18]
miRNA	miR-145	非小细胞肺癌	临床前研究	[19]
	miR-145	卵巢癌	临床前研究	[13]
	miR-29a，miR-330-5p	胰腺癌	临床前研究	[20]
	miR-1226-3p	侵袭性乳腺癌症	临床前研究	[21]
	miR-150	胰腺癌	临床前研究	[15]
	miR-200c	胰腺癌	临床前研究	[22]

抑制剂种类	药物名称	肿瘤类型	研究现状	参考文献
多肽	GO-203	人十二指肠腺癌	临床前研究	[10]
		食管鳞状细胞癌	临床前研究	[11, 16]
		尿路上皮癌	临床前研究	[12]
		急性髓系白血病	临床前研究	[17-18]
miRNA	miR-145	非小细胞肺癌	临床前研究	[19]
	miR-145	卵巢癌	临床前研究	[13]
	miR-29a，miR-330-5p	胰腺癌	临床前研究	[20]
	miR-1226-3p	侵袭性乳腺癌症	临床前研究	[21]
	miR-150	胰腺癌	临床前研究	[15]
	miR-200c	胰腺癌	临床前研究	[22]

治疗措施	药物名称	肿瘤类型	研究现状	参考文献/临床试验编号
单克隆抗体	TAB004	胰腺导管腺癌	临床前研究	[23]
	Gatipotuzumab	复发性卵巢上皮癌	临床Ⅱ期	[32]/NCT01899599
	PankoMab-GEX	TA-MUC1阳性癌症	临床Ⅰ期	[25]/NCT0122624
	Oregovomab	复发性卵巢癌	临床Ⅱ期	NCT05335993
ADC疗法	16A+MMAE	非小细胞肺癌	临床前研究	[33]
	SAR566658	胰腺癌、宫颈癌、膀胱癌、卵巢癌与乳腺癌	临床前研究	[28]
		恶性肿瘤	临床Ⅰ期	NCT01156870
		三阴性乳腺癌	临床Ⅱ期	NCT02984683
	3D1-MMAE	肺癌、三阴性乳腺癌	临床前研究	[34]
	BM7-PE MUC1	结直肠癌	临床Ⅱ期	NCT04550897
	M1231	实体瘤	临床Ⅰ期	NCT04695847
	DMUC5754A	卵巢癌、不可切除胰腺癌	临床Ⅰ期	[30]
CAR-T 疗法	MUC28z CAR T	三阴性乳腺癌症	临床前研究	[35]
	CAR-MUC1-IL22 T细胞	头颈部鳞状细胞癌	临床前研究	[36]
	huMNC2-CAR44 T细胞	转移性乳腺癌	临床Ⅰ期	NCT04020575
	JCAR020	实体瘤	临床Ⅰ期	NCT02498912

治疗措施	药物名称	肿瘤类型	研究现状	参考文献/临床试验编号
单克隆抗体	TAB004	胰腺导管腺癌	临床前研究	[23]
	Gatipotuzumab	复发性卵巢上皮癌	临床Ⅱ期	[32]/NCT01899599
	PankoMab-GEX	TA-MUC1阳性癌症	临床Ⅰ期	[25]/NCT0122624
	Oregovomab	复发性卵巢癌	临床Ⅱ期	NCT05335993
ADC疗法	16A+MMAE	非小细胞肺癌	临床前研究	[33]
	SAR566658	胰腺癌、宫颈癌、膀胱癌、卵巢癌与乳腺癌	临床前研究	[28]
		恶性肿瘤	临床Ⅰ期	NCT01156870
		三阴性乳腺癌	临床Ⅱ期	NCT02984683
	3D1-MMAE	肺癌、三阴性乳腺癌	临床前研究	[34]
	BM7-PE MUC1	结直肠癌	临床Ⅱ期	NCT04550897
	M1231	实体瘤	临床Ⅰ期	NCT04695847
	DMUC5754A	卵巢癌、不可切除胰腺癌	临床Ⅰ期	[30]
CAR-T 疗法	MUC28z CAR T	三阴性乳腺癌症	临床前研究	[35]
	CAR-MUC1-IL22 T细胞	头颈部鳞状细胞癌	临床前研究	[36]
	huMNC2-CAR44 T细胞	转移性乳腺癌	临床Ⅰ期	NCT04020575
	JCAR020	实体瘤	临床Ⅰ期	NCT02498912

疫苗种类	产品名称	肿瘤类型	研究现状	参考文献/临床试验编号
DNA疫苗	pVAX1-MUC1-VNTR₆DNA疫苗	胰腺癌	临床前研究	[37]
DNA疫苗	survivin/ MUC1 (MS)-IL-2-CpG	结直肠癌	临床前研究	[52]
病毒载体疫苗	TG4010	前列腺癌、肾癌	临床Ⅱ期	[53]
	TG4010	非小细胞肺癌	临床Ⅱ/Ⅲ期	[41]
	ETBX-061	前列腺癌	临床Ⅰ期	[54]
	ETBX-061	结直肠癌、胆管癌	临床Ⅰ期	[42]
树突状细胞疫苗	CVac	卵巢癌	临床Ⅱ期	[43]
树突状细胞疫苗	CVac	胰腺癌	临床Ⅱ期	NCT02310971
亚单位疫苗	L-BLP25	乳腺癌	临床Ⅱ期	[55]
		非小细胞肺癌	临床Ⅱ/Ⅲ期	[56-57]
		多发性骨髓瘤	临床Ⅱ期	[58]
		转移性结直肠癌	临床Ⅱ期	[59-60]
		前列腺癌	临床Ⅱ期	NCT01496131
	MUC1-Poly-ICLC	结直肠癌	临床Ⅰ/Ⅱ期	[61]
	ImMucin	多发性骨髓瘤	临床Ⅰ/Ⅱ期	[47]
糖肽疫苗	ONT-10	乳腺癌、卵巢癌	临床Ⅰ期	NCT02270372
	ONT-10	实体瘤	临床Ⅰ期	NCT01556789
	Theratope	转移性乳腺癌	临床Ⅲ期	[62-63]

黏蛋白在肿瘤免疫治疗中的研究进展

Research Progress of Mucin in Tumor Immunotherapy

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