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Lyons et al. Cancer Drug Resist 2021;4:745-54 Cancer
DOI: 10.20517/cdr.2021.37
Drug Resistance

Opinion Open Access

Advances in preclinical evaluation of experimental
antibody-drug conjugates

Scott K. Lyons, Dennis Plenker, Lloyd C. Trotman

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Correspondence to: Dr. Scott K. Lyons, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. E-
mail: slyons@cshl.edu; Dr. Lloyd C. Trotman, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724,
USA. E-mail: trotman@cshl.edu
How to cite this article: Lyons SK, Plenker D, Trotman LC. Advances in preclinical evaluation of experimental antibody-drug
conjugates. Cancer Drug Resist 2021;4:745-54. https://dx.doi.org/10.20517/cdr.2021.37

Received: 30 Apr 2021 First Decision: 8 Jun 2021 Revised: 17 Jun 2021 Accepted: 23 Jun 2021 First online: 4 Jul 2021

Academic Editor: Godefridus J. Peters Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
The ability to chemically modify monoclonal antibodies with the attachment of specific functional groups has
opened up an enormous range of possibilities for the targeted treatment and diagnosis of cancer in the clinic. As
the number of such antibody-based drug candidates has increased, so too has the need for more stringent and
robust preclinical evaluation of their in vivo performance to maximize the likelihood that time, research effort, and
money are only spent developing the most effective and promising candidate molecules for translation to the clinic.
Concurrent with the development of antibody-drug conjugate (ADC) technology, several recent advances in
preclinical research stand to greatly increase the experimental rigor by which promising candidate molecules can
be evaluated. These include advances in preclinical tumor modeling with the development of patient-derived tumor
organoid models that far better recapitulate many aspects of the human disease than conventional subcutaneous
xenograft models. Such models are amenable to genetic manipulation, which will greatly improve our
understanding of the relationship between ADC and antigen and stringently evaluate mechanisms of therapeutic
response. Finally, tumor development is often not visible in these in vivo models. We discuss how the application of
several preclinical molecular imaging techniques will greatly enhance the quality of experimental data, enabling
quantitative pre- and post-treatment tumor measurements or the precise assessment of ADCs as effective
diagnostics. In our opinion, when taken together, these advances in preclinical cancer research will greatly improve
the identification of effective candidate ADC molecules with the best chance of clinical translation and cancer
patient benefit.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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