Challenges of Antibody Drug Conjugates in Cancer Therapy: Current Understanding of Mechanisms and Future Strategies

Molecular Drug Disposition (M Hu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Molecular Drug Disposition

Abstract

Purpose of Review

Antibody drug conjugates (ADCs) are a class of powerful anti-cancer therapeutics composed of a potent cytotoxic drug, a cancer cell-targeting monoclonal antibody (mAb), and a linker connecting the drug to the antibody. Despite often being referred to as magic bullet, ADCs are still far from perfect and further improvements are required to enhance the therapeutic potential of ADCs.

Recent Findings

The goal of ADCs is to improve the therapeutic index of cytotoxic drugs. Nevertheless, many of the current ADCs still have relatively narrow therapeutic index and limited clinical success. This manuscript is a comprehensive review of the up-to-date knowledge on mechanism of action of ADCs, key factors that affect the safety and efficacy of ADCs, and the challenges and new strategies associated with rational design of ADCs.

Summary

The major challenges of developing an effective ADC include selection of the appropriate target antigens, the chemically stable linkers, and the highly potent cytotoxic drugs. Each component of an ADC must be optimized to fully realize the goal of improvement of efficacy and tolerability of the ADC. Understanding of these key determining factors can provide guidance for the development of these complex molecules.

Keywords

Antibody drug conjugates (ADCs) Target selection Therapeutic index Cytotoxicity Cancer 

Notes

Compliance with Ethical Standards

Conflict of Interest

JHL is an independent consultant of DMPK; YG and WW are employees of Janssen Research & Development, LLC. The opinions expressed in this publication are those of the authors and do not necessarily reflect those of the company who employs them.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biopharm Consulting Partners, LLCAmblerUSA
  2. 2.Biologics Development SciencesJanssen R&DSpring HouseUSA

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