Novel Toll-Like Receptor (TLR) 7/8 Agonist Antibody-Drug Conjugates

Background

Toll-like receptor (TLR) agonists are immunostimulants that are often used as vaccine adjuvants. They activate the adaptive immune system leading to a more robust antiviral effect, and can also be used to unmask the immunosuppressive tumor environment and initiate a robust anti‐tumor response by the immune system. A number of TLR 7/8 agonists have been developed for anticancer and antiviral applications, including the approved compound imiquimod.

Technology Overview

A current limitation of TLR agonist use is that their systemic delivery can result in whole‐body immunostimulation, leading to acute toxicity from a cytokine‐storm event. To circumvent this, Binghamton University researchers have developed antibody-drug conjugates (ADCs) of TLR 7/8 agonists for targeting select tumor cells. Specifically, they have developed novel TLR 7/8 agonists with enhanced immunostimulatory potency relative to imiquimod and resiquimod. The TLR agonist ADCs, conjugated via cleavable linkers, demonstrated targeting specificity, immunostimulatory activity, plasma stability, and lysosomal drug release.

Benefits

• Higher immunostimulatory potency than imiquimod and resiquimod
• Targeted TLR agonist delivery
• Reduced risk of hyper-inflammatory responses and off-target effects

Applications

• Anti-tumor therapies, including those for breast cancer
• Antiviral therapies

Opportunity

• Available for licensing or collaboration