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Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tu...

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Autores principales: Kim, Eunhee G., Kim, Kristine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624065/
https://www.ncbi.nlm.nih.gov/pubmed/26535074
http://dx.doi.org/10.4062/biomolther.2015.116
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author Kim, Eunhee G.
Kim, Kristine M.
author_facet Kim, Eunhee G.
Kim, Kristine M.
author_sort Kim, Eunhee G.
collection PubMed
description Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris(®) (anti-CD30-drug conjugate) and Kadcyla(®) (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.
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spelling pubmed-46240652015-11-03 Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics Kim, Eunhee G. Kim, Kristine M. Biomol Ther (Seoul) Invited Review Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris(®) (anti-CD30-drug conjugate) and Kadcyla(®) (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed. The Korean Society of Applied Pharmacology 2015-11 2015-11-01 /pmc/articles/PMC4624065/ /pubmed/26535074 http://dx.doi.org/10.4062/biomolther.2015.116 Text en Copyright ©2015, The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Review
Kim, Eunhee G.
Kim, Kristine M.
Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title_full Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title_fullStr Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title_full_unstemmed Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title_short Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
title_sort strategies and advancement in antibody-drug conjugate optimization for targeted cancer therapeutics
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624065/
https://www.ncbi.nlm.nih.gov/pubmed/26535074
http://dx.doi.org/10.4062/biomolther.2015.116
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