Coya Therapeutics Successfully Engineers Regulatory T Cell (Treg) Derived Exosomes with CTLA-4 Protein to Selectively Target Immune Cells with Potential to Deliver Targeted Therapies Across Multiple Diseases

  • Using proprietary exosome tethering modification technology, Treg derived exosomes were engineered with a surface protein, cytotoxic T lymphocyte associated protein 4 (CTLA-4) to increase selective targeting to immune cells;
  • This patented technology requires no genetic modifications, overcomes known limitations of exosome manipulation, and enables tethering of multiple potential proteins to an exosome surface and loading of therapeutic cargo in the exosome interior;
  • CTLA-4-engineered Treg exosomes (CTLA-4-Treg exosomes) dramatically increased targeting of, binding to, internalization of, and uptake into immune cells including macrophages and T cells;
  • This technology can serve as a platform to engineer the exosome surface with proteins of interest to target specific cell and tissue types to potentially treat epitope driven autoimmune diseases and cancer

Coya Therapeutics, Inc. (“Coya” or the “Company”), a clinical-stage biotechnology company developing multiple therapeutic platforms intended to enhance Treg function, including biologics and cell therapies, announced that Dr. Phil Campbell, Professor of Biomedical Engineering at CMU, presented his talk, “Rapid Functionalization of Treg Exosomes for Targeted Immunotherapy” at the 5th Exosome Based Therapeutic Development Summit in Boston, MA this morning (September 7, 2023). The presentation can be accessed here.

Coya and CMU entered into a Research Collaboration Agreement and Option Agreement in 2022 to develop a unique patented technology intended to advance the potential use of exosomes for the treatment of diseases of unmet need.

In this study, it was demonstrated that by using a proprietary cholesterol DNA tether technology, Treg exosome membranes could be engineered to controllably immobilize CTLA-4, a membrane surface active protein, onto the Treg exosome surface resulting in stable CTLA-4-Treg exosomes. It was also demonstrated that CTLA-4-Treg exosomes exhibited far better cell uptake then non-modified Treg EVs in representative immune cells, macrophages (J7774 murine cell line) and T-cells (human Jurket cell line).

Previously, using the same technology, CMU demonstrated applications in Oncology by engineering mesenchymal derived exosomes with an immunomodulatory apoptotic inducing protein, Fas Ligand (FAS-L). The results demonstrate that targeted delivery of FASL-exosomes substantially increases its therapeutic effect with enhanced apoptosis in tumor cells and suppression of alloreactive T cells in mice, while minimizing potential off target effects. This publication is available here.

Tregs are important immunomodulatory cells, with a key role controlling inflammation, enabling self-tolerance, and promoting regenerative processes. Treg-derived exosomes share many of the properties of the parent Treg cells making them able to modulate physiological and pathophysiological processes. The proprietary technology generates Exosome Polymer Hybrids (EPHs) which allow for efficient and versatile method of engineering and customizing cargos of Treg-derived exosomes using oligonucleotide tethers. Delivering EPHs to sites of inflammation or epitopes that drive specific diseases, while delivering customized loads, enables the next generation of selectively targeted and potent Treg-derived exosomes.

Engineered exosomes may have multiple advantages, including low immunogenicity, improved stability, increased plasma retention after systemic delivery and increased residence time following local delivery, enhanced biodistribution, improved cell binding and uptake, and enhanced targeted therapeutic response.

Dr. Fred Grossman, President and Chief Medical Officer of Coya stated,“This proprietary technology expands Coya’s pipeline to include autoimmune disorders and cancer. These engineered exosomes are a cell – free drug delivery system without genetic modification that can travel throughout the body unimpeded, including through the blood brain barrier, to provide specific targeted therapies.”


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