Alternative to Antibody Drug Conjugates

Background:

While ADCs have seen some success in the market, toxicity issues have limited the class from reaching its full potential.  Toxicity of these agents stems from exposure of their payloads (e.g. auristatin), primarily due to premature (i.e. off-target) release.  For example, ADCs comprising linkers that are designed to be highly stable have demonstrated premature cleavage by neutrophil elastase, leading to neutropenia, a dose-limiting toxicity.  Even ADCs comprising non-cleavable linkers have been observed to exhibit toxicities due to non-specific interactions between the exposed payload and healthy cells.  Alternatives are needed that overcome these limitations and deliver on the promise of safe, targeted and efficacious delivery of drugs to cells of interest.

Technology Overview:

This University at Buffalo invention provides a novel approach to the targeted delivery of drug payloads to cancer cells.  Specifically, high affinity anti-payload antibody compositions that also comprise a targeting ligand have been developed.  These compositions avoid cleavage- and exposure-related issues because of their high affinity binding, thus eliminating the need for a linker (or conjugation step), and concealing of the payload within the antibody binding interface, respectively.

Advantages:

(relative to Antibody Drug Conjugates)

• Decreased systemic exposure of toxic payload
• Lower off-target release
• Simpler manufacturing
• Potentially greater therapeutic window

Applications:

• Oncology

Intellectual Property:

U.S. Provisional Patent Application 63/469,157 filed 26 May 2023.

Stage of Development:

In vivo xenograft studies

Licensing Status:

Available for licensing or collaboration.

Publication Links:

No publications to date