Small Molecule Immunopotentiator Conjugates of NF-KB Activators as Adjuvants With Enhanced Efficacy And Reduced Toxicity

SUMMARY

• Imidazoquinolinone derivatives that activate Toll-like receptor (TLR) 7/8 are small molecule immune potentiators (SMIPs) that have potent activity as vaccine adjuvants and as anti-tumor agents. However, these molecules have high bioavailability that results in unacceptable levels of systemic inflammation due to adjuvant toxicity greatly limiting their use.

• The faculty inventor developed an alternative to small molecule adjuvant formulation where a TLR7/8 activating imidazoquinolinone is covalently linked to a NF-κB potentiator – altering the response that the molecule directly elicits from immune cells. This invention involves synthesis of novel imidazoquinolinone-NF-κB potentiator dimers.

• With ovalbumin as a model antigen the inventors vaccinated mice and showed that these dimers reduce systemic toxicity to baseline levels while maintaining the adjuvanticity in a vaccine formulation. Additionally, they showed that select dimers increased survivability in a CT26 WT mouse colon carcinoma tumor model while eliciting low adjuvant toxicity.

FIGURE

ADVANTAGES

ADVANTAGES

• Significantly reduces systemic toxicity post in-vivo administration
• Enhances efficacy

APPLICATIONS

• Combines small molecule agonists with small molecule immunopotentiators to generate new molecules that serve as potent non-toxic adjuvants.

• Broadens the use of SMIPs both as adjuvants in vaccines and in immunotherapy formulations for in-vivo administration of immune activators. 

October 31, 2023

Proof of concept

Patent Pending

Licensing,Co-development

Aaron Esser-Kahn