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The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.

ABSTRACT: Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses of the cytotoxic drug to be administered, potentially increasing efficacy. They are currently among the most promising drug classes in oncology, with efforts to expand their application for nononcological indications and in combination therapies. Here we provide a detailed overview of the recent advances in ADC research and consider future directions and challenges in promoting this promising platform to widespread therapeutic use. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, and analyze the publication landscape of recent research to reveal the exploration trends in published documents and to provide insights into the scientific advances in the area. We also discuss the evolution of the key concepts in the field, the major technologies, and their development pipelines with company research focuses, disease targets, development stages, and publication and investment trends. A comprehensive concept map has been created based on the documents in the CAS Content Collection. We hope that this report can serve as a useful resource for understanding the current state of knowledge in the field of ADCs and the remaining challenges to fulfill their potential.

SUBMITTER: Sasso JM

PROVIDER: S-EPMC10655051 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.

Sasso Janet M JM Tenchov Rumiana R Bird Robert R Iyer Kavita A KA Ralhan Krittika K Rodriguez Yacidzohara Y Zhou Qiongqiong Angela QA

Bioconjugate chemistry 20231011 11

Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses of the cytotoxic drug to be administered, potentially increasing efficacy. They are currently among the most promising drug classes in oncology, with efforts to expand their application for nononcological indications and in combina ...[more]

PMID: 37821099

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Project description:Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these 'off-target effects', such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.

Dataset Information

The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.

Publications

The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.

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