改革实体瘤治疗:小规格抗体药物共轭物的新兴潜力

Q2 Medicine Antibody Therapeutics Pub Date : 2024-02-16 DOI:10.1093/abt/tbae005
Xiaojie Ma, Mingkai Wang, Tianlei Ying, Yan-ling Wu
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引用次数: 0

摘要

摘要 近年来,16 种用于治疗恶性肿瘤的抗体药物共轭物 (ADC) 获得批准,从而验证了抗体药物共轭物 (ADC) 的巨大疗效。然而,要实现 ADC 在临床上的最大应用,需要克服现有的挑战,主要是针对实体瘤时肿瘤穿透能力的限制。为了解决肿瘤穿透能力不理想的问题,人们利用经过设计的小型化抗体片段来组装 ADC。抗体片段-药物共轭物因其分子尺寸较小,在有效递送细胞毒性药物方面大有可为,从而带来卓越的治疗效果。本综述将重点介绍目前利用 6 至 80 kDa 的较小抗体形式开发新型 ADC 的进展,特别强调已广泛应用于新型 ADC 设计的单域抗体。此外,还讨论了优化临床转化的策略,包括延长半衰期、加速内化和降低免疫原性。
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Reforming solid tumor treatment: the emerging potential of smaller format antibody-drug conjugate
Abstract In recent years, substantial therapeutic efficacy of antibody-drug conjugates (ADCs) has been validated through approvals of 16 ADCs for the treatment of malignant tumors. However, realization of the maximum clinical use of ADCs requires surmounting extant challenges, mainly the limitations in tumor penetration capabilities when targeting solid tumors. To resolve the hurdle of suboptimal tumor penetration, miniaturized antibody fragments with engineered formats have been harnessed for ADC assembly. By virtue of their reduced molecular sizes, antibody fragment-drug conjugates hold considerable promise for efficacious delivery of cytotoxic agents, thus conferring superior therapeutic outcomes. This review will focus on current advancements in novel ADC development utilizing smaller antibody formats from ~6 to 80 kDa, with particular emphasis on single-domain antibodies, which have been widely applied in novel ADC design. Additionally, strategies to optimize clinical translation are discussed, including half-life extension, acceleration of internalization, and reduction of immunogenic potential.
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来源期刊
Antibody Therapeutics
Antibody Therapeutics Medicine-Immunology and Allergy
CiteScore
8.70
自引率
0.00%
发文量
30
审稿时长
8 weeks
期刊最新文献
AI-based antibody discovery platform identifies novel, diverse, and pharmacologically active therapeutic antibodies against multiple SARS-CoV-2 strains. FcRider: a recombinant Fc nanoparticle with endogenous adjuvant activities for hybrid immunization. A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response. Correction to: A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications. The process using a synthetic library that generates multiple diverse human single domain antibodies.
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