An Insight into FDA Approved Antibody-Drug Conjugates for Cancer Therapy.

Paul W R Harris,Iman Kavianinia,Margaret A Brimble,Juliana T W Tong

doi:10.3390/molecules26195847

Paul W R Harris, Iman Kavianinia + Show 2 more

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https://doi.org/10.3390/molecules26195847

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Abstract

The large number of emerging antibody-drug conjugates (ADCs) for cancer therapy has resulted in a significant market ‘boom’, garnering worldwide attention. Despite ADCs presenting huge challenges to researchers, particularly regarding the identification of a suitable combination of antibody, linker, and payload, as of September 2021, 11 ADCs have been granted FDA approval, with eight of these approved since 2017 alone. Optimism for this therapeutic approach is clear, despite the COVID-19 pandemic, 2020 was a landmark year for deals and partnerships in the ADC arena, suggesting that there remains significant interest from Big Pharma. Herein we review the enthusiasm for ADCs by focusing on the features of those approved by the FDA, and offer some thoughts as to where the field is headed.

Highlights

Paul Ehrlich’s vision of a rationally targeted strategy to eliminate disease, whether it be microbes or malignant cells, has driven research over the past century, creating a targeted cancer therapy revolution [1]
Over 80 years following Ehrlich’s fundamental realization, and supported by the successful development of chemotherapy in the 1940s [2] and monoclonal antibodies in the 1970s [3], in 1983 the first successful antibody-drug conjugate (ADC) human clinical trial began using an anti-carcinoembryonic antibody tethered to vindesine [4]
ADCs are amongst the fastest growing drug classes in oncology, as they combine the best features of monoclonal antibodies (mAbs) and small molecule drugs, creating a single moiety that is highly specific and cytotoxic

Summary

Introduction

Paul Ehrlich’s vision of a rationally targeted strategy to eliminate disease, whether it be microbes or malignant cells, has driven research over the past century, creating a targeted cancer therapy revolution [1]. These therapeutic entities are considered the “homing missiles” of cancer therapy, and are composed of three key elements: a monoclonal antibody that selectively binds to an antigen on the tumor cell surface, a cytotoxic drug payload, and a cleavable or non-cleavable linker, see Figure 1 [5,6,7]. ADCs are designed to deliver the toxic payload selectively to cells expressing the target antigen.

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