Alfred Zippelius,Sara M Tolaney,Paolo Tarantino,Joseph P Balthasar,Greg M Thurber
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引用次数: 0
Abstract
After decades of investment, antibody-drug conjugates (ADCs) are finally demonstrating their potential, marked by a growing number of clinical approvals, applications in earlier lines of treatment and integration into drug combinations, including immunotherapies. This progress has spurred investment in developing new ADCs and expanding the use of approved ADCs in clinical practice. The design of ADCs is complex, involving multiple molecular components that interact with both tumour and host tissue microenvironments. In this Review, we explore the molecular and immunological factors influencing ADC efficacy and toxicity. We describe how the molecular components of ADCs determine their systemic, tissue and cellular distribution, which ultimately dictates therapeutic efficacy. These interactions also determine the toxicity profile and set limitations on maximum dosing. Finally, we discuss the impact of ADC treatment on immune cells, emphasizing the distinct but interconnected roles of immunogenic cell death, activation of immune cells such as dendritic cells and antibody-Fc interactions. These mechanisms are crucial for increasing efficacy beyond the direct cytotoxic effects of the payload. By providing insights into the intricate interactions of ADCs, this Review aims to inform the rational design of combination therapies and guide the development of the next generation of clinically effective ADCs.
期刊介绍:
Nature Reviews Cancer, a part of the Nature Reviews portfolio of journals, aims to be the premier source of reviews and commentaries for the scientific communities it serves. The correct abbreviation for abstracting and indexing purposes is Nat. Rev. Cancer. The international standard serial numbers (ISSN) for Nature Reviews Cancer are 1474-175X (print) and 1474-1768 (online). Unlike other journals, Nature Reviews Cancer does not have an external editorial board. Instead, all editorial decisions are made by a team of full-time professional editors who are PhD-level scientists. The journal publishes Research Highlights, Comments, Reviews, and Perspectives relevant to cancer researchers, ensuring that the articles reach the widest possible audience due to their broad scope.