Description:
Faculty members at the University of Texas Health Science Center at Houston have developed a novel chemical linker for constructing antibody-drug conjugates (ADCs). While traditional ADC linkers can only load a single payload molecule, the developed linker has the ability to load two identical or different drug payloads. Doubling the number of payloads increases the drug-to antibody ratio which can lead to enhanced potency in cell viability assays (as shown in animal model experiments). The novel linker system provides the opportunity to revisit payloads that are mechanistically attractive; payloads that have been formerly excluded due to their suboptimal potencies in the ADC format. The linkers also allow the delivery of two different payloads to the same cancer cell, allowing overall efficacy and reducing the development of resistant cancer cells.
The collaborators have also developed novel chemical linkers for constructing ADCs and other drug conjugates for targeted cancer therapy. The chemical linkers have a unique proprietary sequence that provides significantly improved stability in the circulation in animal models. The circulation stability enables the quicker release of drugs inside the target tumor cells.
Publications:
Glutamic Acid-Valine-Citrulline Linkers Ensure Stability and Efficacy of Antibody-Drug Conjugates in Mice.
https://www.nature.com/articles/s41467-018-04982-3
Antibody-Drug Conjugates: Recent Advances in Conjugation and Linker Chemistries.
https://www.ncbi.nlm.nih.gov/pubmed/27743348
Enzymatic Conjugation Using Branched Linkers for Constructing Homogeneous Antibody–Drug Conjugates with High Potency.
http://pubs.rsc.org/en/content/articlelanding/2017/ob/c7ob01027c#!divAbstract
Inventors:
Kyoji Tsuchikama
Yasuaki Anami
Chisato Tsuchikama
Ningyan Zhang
Zhiqiang An
Intellectual Property Status:
PCT/US2018/034363 filed and available for licensing, exclusive or non-exclusive.