2021-102 – Single-chain Immune Modulators for use in Adenovirus-based Gene Therapy

Abstract

Transplantation of organs and tissues is a viable treatment option for many patients with chronic diseases. However, immune rejection is a major obstacle that often requires a lifetime of repeated transplantation or use of immunosuppressive drugs to help counteract rejection.

In recent years, the tolerogenic molecule, HLA-G, has received much attention as a possible new therapeutic for use in transplantations. While typically produced as a monomer, most of its biological functions are attributed to the disulfide linked dimer form which provides for enhanced receptor binding and intracellular signaling. To facilitate the therapeutic use of HLA-G proteins, efforts are underway to simplify its delivery.

This invention is comprised of a platform technology of single chain immune modulators (scIMs) capable of functioning as dimeric protein complexes as a single polypeptide. Specifically, a monomeric fusion protein has been generated providing for the single gene delivery of HLA-G dimer, bypassing the slow kinetics required with native disulfide bond formation. Such a technology has potential to provide for exogenously expressed HLA-G as a constitutive immune modulator in place of a lifetime of anti-rejection drugs.

Reference Number: 2021-102

Market Applications:

  • Immune modulator;
  • Adenovirus-based Gene Therapy;
  • Natural alternative to immunosuppressive drugs.

Features, Benefits, and Advantages:

  • Use of Adeno Associated Virus Construct (AAC)-scIMs requires less virus since the kinetically slowest steps of HLA-G dimerization are eliminated;
  • Construct design alleviates requirement for the association of HLA-based molecules with Beta-2-microglobulin (B2M), another rate limiting step for HLA-G fusion;
  • Preliminary data in vivo data in neovascularization assay is promising.

Intellectual Property:A U.S. Provisional Patent Application (63/285,167) was filed on December 2, 2021.

Development Stage:The scIMs gene has been successfully built and shown to produce soluble protein in cell culture. In addition, the immunological activity has demonstrated comparable activity to wild type HLA-G in a sodium hydroxide corneal burn-induced neovascularization assay.

Contact Information

Name: Hutton Jones

Email: william.h.jones@ttu.edu

Phone: 806-834-5756