Challenges and Therapeutic Strategies for Bispecific T Cell-redirecting Antibodies in Tumor Treatment

doi:10.13523/j.cb.2302011

China Biotechnology

2023, Vol. 43

Issue (6): 31-42 DOI: 10.13523/j.cb.2302011

Challenges and Therapeutic Strategies for Bispecific T Cell-redirecting Antibodies in Tumor Treatment

QIN Xiao-jing,LIU Xue,LUO Wen-xin^**(

)

National Institute of Diagnostics and Vaccine Development in Infections Diseases, School of Public Health, Xiamen University, Xiamen 361102, China

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Abstract

Bispecific T cell-redirecting antibodies are designed to bind to selected tumor-associated antigens and to CD3 of the T cell receptor. Linking tumor cells and T cells results in activating T cells and inducing targeted T cell-mediated killing of the recognized tumor cells. They have become one of the most promising approaches in tumor immunotherapy. Although this therapy was successfully applied in hematological malignancies therapy, no significant progress in the treatment of solid tumors have been achieved. In this article, we review the major challenges of bispecific T cell-redirecting antibodies, and novel strategies to overcome these hurdles as well as to broaden the indications for this therapy, particularly to solid cancers.

Key words： Bispecific T cell-redirecting antibodies Immunotherapy Tumor

Received: 06 February 2023 Published: 04 July 2023

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Cite this article:

QIN Xiao-jing, LIU Xue, LUO Wen-xin. Challenges and Therapeutic Strategies for Bispecific T Cell-redirecting Antibodies in Tumor Treatment. China Biotechnology, 2023, 43(6): 31-42.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2302011 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I6/31

Table 1 Bispecific antibodies approved for marketing

药物名称	靶点	适应证	临床阶段	临床编号	地区
Linvolseltamab	BCMA×CD3	多发性骨髓瘤	临床Ⅰ期	NCT05137054	希腊、西班牙
Teclistamab	BCMA×CD3	血液恶性肿瘤	临床Ⅰ期	NCT03145181	美国、法国、荷兰、西班牙
Elranatamab	BCMA×CD3	多发性骨髓瘤	临床Ⅰ期	NCT05675449	美国
			临床Ⅱ期	NCT05090566	美国、加拿大
				NCT05228470	中国
				NCT05014412	美国、日本、中国、英国
			临床Ⅲ期	NCT05020236	阿根廷、澳大利亚、奥地利、比利时、巴西、加拿大、中国、捷克、芬兰、法国、德国、希腊、意大利、日本、韩国、墨西哥、荷兰、新西兰、挪威、波兰、西班牙、瑞典、土耳其、英国
				NCT05317416	澳大利亚、奥地利、比利时、加拿大、捷克、芬兰、法国、德国、希腊、匈牙利、印度、以色列、意大利、日本、韩国、荷兰、挪威、波兰、西班牙、瑞典、中国、土耳其
EGFR BAT	EGFR×CD3	局部晚期胰腺癌	临床Ⅰ期	NCT03269526	美国
		转移性胰腺癌	临床Ⅱ期
ISB 1342	CD38×CD3	复发/难治性多发性骨髓瘤	临床Ⅰ期	NCT03309111	美国、法国
Talquetamab	GPRC5D×CD3	复发/难治性多发性骨髓瘤	临床1期	NCT04773522	日本
		血液恶性肿瘤	临床Ⅰ期	NCT04634552	美国、比利时、西班牙
			临床Ⅰ期	NCT03399799	美国、比利时、荷兰、西班牙
Teclistamab	BCMA×CD3	复发/难治性多发性骨髓瘤	临床Ⅰ/Ⅱ期	NCT04696809	日本
		血液恶性肿瘤	临床Ⅱ期	NCT04557098	美国
Odronextamab	CD20×CD3	B细胞非霍奇金淋巴瘤	临床Ⅱ期	NCT03888105	美国、中国、法国、德国、加拿大、澳大利亚、意大利、日本、韩国、波兰、新加坡、西班牙、英国
REGN5459/ REGN5458	BCMA×CD3	慢性肾病	临床Ⅰ/Ⅱ期	NCT05092347	美国、加拿大、中国、比利时、法国、德国、意大利、荷兰、西班牙、瑞典、英国
Y150	CD38×CD3	复发/难治性多发性骨髓瘤	临床Ⅰ期	NCT05011097	中国
RGV004	CD19×CD3	难治性/复发性B细胞淋巴瘤	临床Ⅰ期	NCT04887025	中国
EMB-07	ROR1×CD3	高级/转移性实体肿瘤	临床Ⅰ期	NCT05607498	澳大利亚、中国
AMG 340	PSMA×CD3	转移性抗阉割前列腺癌	临床Ⅰ期	NCT04740034	美国
TNB-486	CD19×CD3	B细胞非霍奇金淋巴瘤	临床Ⅰ期	NCT04594642	美国、韩国
		弥漫性大B细胞淋巴瘤
		高级别B细胞淋巴瘤
		滤泡性淋巴瘤
GEN1047	B7-H4×CD3	乳腺癌	临床Ⅰ/Ⅱ期	NCT05180474	丹麦、法国、西班牙
		子宫癌
		卵巢癌
		鳞状非小细胞肺癌
Mosunetuzumab	CD20×CD3	大B细胞淋巴瘤	临床Ⅱ期	NCT04889716	美国
ARB202	CDH17×CD3	胃肠道癌	临床Ⅰ期	NCT05411133	澳大利亚、中国、新加坡
		胆管癌
		肝癌
		结直肠癌
		胰腺癌
		胃癌
JNJ-75348780	CD22×CD3	非霍奇金淋巴瘤	临床Ⅰ期	NCT04540796	美国、法国、以色列、韩国、西班牙、中国、英国
		慢性淋巴细胞白血病
Odronextamab	CD20×CD3	非霍奇金淋巴瘤	临床Ⅰ期	NCT02290951	美国、法国、德国、以色列、英国
		慢性淋巴细胞白血病
MGD024	CD123×CD3	急性/慢性骨髓白血病	临床Ⅰ期	NCT05362773	美国
		骨髓增生异常综合征
		经典霍奇金淋巴瘤
CC-1	PSMA×CD3	前列腺癌复发	临床Ⅰ期	NCT05646550	德国
GB261	CD20×CD3	非霍奇金淋巴瘤	临床Ⅰ/Ⅱ期	NCT04923048	澳大利亚
		慢性淋巴细胞白血病
EMB-06	BCMA×CD3	复发/难治性多发性骨髓瘤	临床Ⅰ/Ⅱ期	NCT04735575	澳大利亚、中国
Vibecotamab	CD123×CD3	急性髓系白血病	临床Ⅱ期	NCT05285813	美国
		骨髓增生异常综合征
Glofitamab	CD20×CD3	复发/难治性淋巴瘤	临床Ⅱ期	NCT04703686	法国

Table 2 Representative clinical trials of bispecific T cell-redirecting antibodies

Fig.1 Formats of different bispecific antibodies

Fig.2 Mechanism of action of T cell redirection bispecific antibodies

Fig.3 Design of probody and functional mechanism

Table 3 Challenges and therapeutic strategies for bispecific T cell-redirecting antibodies


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