Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 16 (5), 315-337

Strategies and Challenges for the Next Generation of Antibody-Drug Conjugates

Affiliations
Review

Strategies and Challenges for the Next Generation of Antibody-Drug Conjugates

Alain Beck et al. Nat Rev Drug Discov.

Abstract

Antibody-drug conjugates (ADCs) are one of the fastest growing classes of oncology therapeutics. After half a century of research, the approvals of brentuximab vedotin (in 2011) and trastuzumab emtansine (in 2013) have paved the way for ongoing clinical trials that are evaluating more than 60 further ADC candidates. The limited success of first-generation ADCs (developed in the early 2000s) informed strategies to bring second-generation ADCs to the market, which have higher levels of cytotoxic drug conjugation, lower levels of naked antibodies and more-stable linkers between the drug and the antibody. Furthermore, lessons learned during the past decade are now being used in the development of third-generation ADCs. In this Review, we discuss strategies to select the best target antigens as well as suitable cytotoxic drugs; the design of optimized linkers; the discovery of bioorthogonal conjugation chemistries; and toxicity issues. The selection and engineering of antibodies for site-specific drug conjugation, which will result in higher homogeneity and increased stability, as well as the quest for new conjugation chemistries and mechanisms of action, are priorities in ADC research.

Similar articles

See all similar articles

Cited by 197 PubMed Central articles

See all "Cited by" articles

References

    1. Sci Rep. 2016 Aug 09;6:30835 - PubMed
    1. Mol Pharm. 2015 Jun 1;12 (6):1863-71 - PubMed
    1. Nat Rev Drug Discov. 2013 May;12(5):329-32 - PubMed
    1. MAbs. 2012 Jul-Aug;4(4):419-25 - PubMed
    1. Oncotarget. 2016 Jan 19;7(3):2555-71 - PubMed

MeSH terms

LinkOut - more resources

Feedback