Reforming solid tumor treatment: the emerging potential of smaller format antibody-drug conjugate

Xiaojie Ma; Mingkai Wang; Tianlei Ying; Yanling Wu

doi:10.1093/abt/tbae005

Reforming solid tumor treatment: the emerging potential of smaller format antibody-drug conjugate

Antib Ther. 2024 Feb 16;7(2):114-122. doi: 10.1093/abt/tbae005. eCollection 2024 Apr.

Authors

Xiaojie Ma¹, Mingkai Wang¹, Tianlei Ying^{1

2}, Yanling Wu^{1

2}

Affiliations

¹ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Shanghai Engineering Research Center for Synthetic Immunology, Fudan University, Shanghai 200032, China.

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.

Keywords: antibody-drug conjugates; single-domain antibody; smaller antibody formats; solid tumors; tumor penetration.

Publication types

Review