Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers
by
, , and
Benjamina Esapa
1,†, 
Jiexuan Jiang
1,†,
Anthony Cheung
1,2,
Alicia Chenoweth
1,2,
David E. Thurston
3,*
and
Sophia N. Karagiannis
1,2,*
1
St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UK
2
Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s Cancer Centre, London SE1 9RT, UK
3
Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9NH, UK
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2023, 15(6), 1845; https://doi.org/10.3390/cancers15061845
Submission received: 9 February 2023
/
Revised: 10 March 2023
/
Accepted: 10 March 2023
/
Published: 19 March 2023
(This article belongs to the Special Issue Antibody-Drug Conjugates—a Coming of Age)
Simple Summary
Antibody-Drug Conjugates (ADCs) provide effective anti-cancer treatments. ADC development requires the identification of appropriate tumour-associated antigens that can be targeted by the ADC to effectively kill cancer cells while minimising damage to healthy cells, thus limiting systemic toxicities. In this review, we examine the attributes of the antigens targeted by the anticancer ADCs that are clinically approved, and consider how these features may contribute to the safety and effectiveness of ADC therapeutics.
Abstract
Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour cells. The recent rapid advancement of the ADC field has so far yielded twelve and eight ADCs approved by the US and EU regulatory bodies, respectively. These serve as effective targeted treatments for several haematological and solid tumour types. In the development of an ADC, the judicious choice of an antibody target antigen with high expression on malignant cells but restricted expression on normal tissues and immune cells is considered crucial to achieve selectivity and potency while minimising on-target off-tumour toxicities. Aside from this paradigm, the selection of an antigen for an ADC requires consideration of several factors relating to the expression pattern and biological features of the target antigen. In this review, we discuss the attributes of antigens selected as targets for antibodies used in clinically approved ADCs for the treatment of haematological and solid malignancies. We discuss target expression, functions, and cellular kinetics, and we consider how these factors might contribute to ADC efficacy.
