Intrinsically immune-tolerant elastin-like recombinant polypeptides used in drug delivery for metabolic diseases and oncology with reduced toxicity.

Almost 80 percent of patients undergoing immunotherapy experience toxicity complications that reduce drug efficacy and over 10 percent of patients experience life-threatening infections.

New immune-tolerant elastin-like polypeptides (iTEPs) can be used as drug carriers without triggering an immune response in both mice and humans (Journal of Drug Targeting. Vol.24, p328-339). This technology has been applied to both drug delivery and immunology. The technology improves delivery of vaccines by conjugating the drug to the iTEP, which then self-assembles into highly stable, non-toxic nanoparticles with improved efficacy (Theranostics. Vol. 6(5), p666-678). The iTEPs are also utilized to target cytotoxic T lymphocytes and improve innate immune response as defense against cancer and infection. An iTEP-delivered CTL vaccine containing a metalloproteinase-9 (MMP-9)-sensitive peptide and a CTL epitope peptide has been developed. The MMP-9-sensitive vaccine increased epitope presentation by 7-fold, increasing the T-cell response by as high as 9.6-fold (Molecular Pharmaceutics, 14(10), 3312-3321). It has also been applied using ?PD-1 antibody for checkpoint inhibition. A fusion protein consisting of a recombinant single-chain variable fragment of ?PD-1 and an amphiphilic immune-tolerant elastin-like polypeptide self-assembles into a nanoparticle, which blocks the PD-1 immune checkpoint in vitro and in vivo (Molecular Pharmaceutics, 14(5), 1494-1500).

Optimization & Testing

• Improves efficacy of peptide therapeutics.
• Eliminates toxicity problems associated with immune checkpoint therapy methods.
• Increases target specificity.
• Adapts to functionality of companion drug.

Aaron Duffy
(801) 585-1377
aaron.duffy@utah.edu