Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Benjamina Esapa; Jiexuan Jiang; Anthony Cheung; Alicia Chenoweth; David E Thurston; Sophia N Karagiannis

doi:10.3390/cancers15061845

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Benjamina Esapa, Jiexuan Jiang, Anthony Cheung, Alicia Chenoweth, David E Thurston, Sophia N Karagiannis

Breast Cancer Now

Research output: Contribution to journal › Review article › peer-review

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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.

Original language	English
Article number	1845
Number of pages	37
Journal	Cancers
Volume	15
Issue number	6
Early online date	19 Mar 2023
DOIs	https://doi.org/10.3390/cancers15061845 https://doi.org/10.3390/cancers15061845
Publication status	Published - 19 Mar 2023

Keywords

Monoclonal Antibodies
mAb—monoclonal antibody
Antibody-drug conjugates (ADC)
Fab regions
ANTIGEN
TARGET
effector functions
IgG
Checkpoint inhibitors
Cancer Immunotherapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers15061845Licence: CC BY
10.3390/cancers15061845

Esapa et al Cancers-15-01845 2023Final published version, 2.13 MBLicence: CC BY
Esapa et al Cancers-15-01845 2023Licence: CC BY

https://www.mdpi.com/2072-6694/15/6/1845Licence: CC BY

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title = "Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers",

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.",

keywords = "Monoclonal Antibodies, mAb—monoclonal antibody, Antibody-drug conjugates (ADC), Fab regions, ANTIGEN, TARGET, effector functions, IgG, Checkpoint inhibitors, Cancer Immunotherapy",

author = "Benjamina Esapa and Jiexuan Jiang and Anthony Cheung and Alicia Chenoweth and Thurston, {David E} and Karagiannis, {Sophia N}",

note = "Funding Information: The research was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC), based at Guy{\textquoteright}s and St. Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London (IS-BRC-1215-20006). The authors acknowledge support from The Biotechnology and Biological Sciences Research Council (BB/T008709/1); Breast Cancer Now (147; KCL-BCN-Q3); the Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London (C604/A25135); The Guy{\textquoteright}s and St. Thomas{\textquoteright}s Foundation Trust Charity (Melanoma Special Fund, 573); CRUK/NIHR in England/DoH for Scotland, Wales, and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); Cancer Research UK (C30122/A11527; C30122/A15774). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2023 by the authors.",

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day = "19",

doi = "10.3390/cancers15061845",

language = "English",

volume = "15",

journal = "Cancers",

issn = "2072-6694",

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T1 - Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

AU - Esapa, Benjamina

AU - Jiang, Jiexuan

AU - Cheung, Anthony

AU - Chenoweth, Alicia

AU - Thurston, David E

AU - Karagiannis, Sophia N

N1 - Funding Information: The research was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC), based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London (IS-BRC-1215-20006). The authors acknowledge support from The Biotechnology and Biological Sciences Research Council (BB/T008709/1); Breast Cancer Now (147; KCL-BCN-Q3); the Cancer Research UK King’s Health Partners Centre at King’s College London (C604/A25135); The Guy’s and St. Thomas’s Foundation Trust Charity (Melanoma Special Fund, 573); CRUK/NIHR in England/DoH for Scotland, Wales, and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); Cancer Research UK (C30122/A11527; C30122/A15774). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Publisher Copyright: © 2023 by the authors.

PY - 2023/3/19

Y1 - 2023/3/19

N2 - 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.

AB - 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.

KW - Monoclonal Antibodies

KW - mAb—monoclonal antibody

KW - Antibody-drug conjugates (ADC)

KW - Fab regions

KW - ANTIGEN

KW - TARGET

KW - effector functions

KW - IgG

KW - Checkpoint inhibitors

KW - Cancer Immunotherapy

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U2 - 10.3390/cancers15061845

DO - 10.3390/cancers15061845

M3 - Review article

C2 - 36980732

SN - 2072-6694

VL - 15

JO - Cancers

JF - Cancers

IS - 6

M1 - 1845

ER -

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Abstract

Keywords

UN SDGs

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