Tregitope

Harnessing natural immune tolerance to treat allergy and autoimmune disease.

A validated, patent-protected platform for antigen-specific tolerance induction — available partnering with EVA Therapeutics.

What are Tregitopes?

Tregitopes are regulatory T cell epitopes — short, naturally occurring peptide sequences found in the constant (Fc) and framework (Fab) regions of immunoglobulin G (IgG). First identified in 2008 in the Fc fragment of IgG, these highly promiscuous MHC class II-binding epitopes specifically activate CD4+CD25hiFoxP3+ natural regulatory T cells (nTregs). When co-incubated with antigen, they suppress effector cytokine secretion, reduce effector T cell proliferation, and increase Treg-associated markers such as FoxP3.[1] Their presence in IgG helps explain the long-recognized tolerogenic effects of intravenous immunoglobulin (IVIG) therapy.[3]

Because Tregitopes act on antigen-presenting cells and regulatory T cells rather than on the target antigen itself, they induce tolerance that is antigen-specific — the immune system is retrained against the co-delivered antigen while global immune competence is preserved.[3] In vivo, Tregitopes are themselves non-immunogenic even when emulsified with strong adjuvants such as complete or incomplete Freund’s adjuvant, a property that supports their safety profile for clinical development.[4]

Allergy

In a well-established murine model of allergic asthma, IgG Tregitopes induced antigen-specific tolerance, demonstrated by adoptive transfer of Tregitope- and allergen-activated Tregs. In both ovalbumin- and ragweed-sensitized animals, Tregitope administration attenuated allergen-induced airway hyperresponsiveness and lung inflammation.[2] Because the tolerogenic action closely parallels that of IVIg, Tregitopes offer a synthetic, scalable alternative to plasma-derived immunoglobulin — and a potential route away from chronic steroid-based management.[2]

Tregitope–allergen fusion constructs have also been explored as a next-generation allergen immunotherapy strategy, designed to redirect pathogenic Th2 responses toward allergen-specific Treg generation.[6]

Autoimmunity and Beyond

In preclinical studies, Tregitopes have prevented, treated, and in some models reversed autoimmune disease; suppressed allo-specific responses in transplant models; inhibited CD8+ T cell responses to recombinant adeno-associated virus (AAV) gene transfer vectors; and induced adaptive Tregs in vivo.[3] Antigen-specific tolerance induction has been demonstrated in a murine model of type 1 diabetes,[5] with additional work reported in experimental colitis and recurrent pregnancy loss.[2]

Taken together, these findings position Tregitopes as a broadly applicable tolerance platform spanning allergy, autoimmunity, transplantation, and the tolerization of protein and gene therapies.[3]

Licensing

Tregitope is a validated, patent-protected platform developed by Anne S. De Groot while she was CEO and CSO of EpiVax. Tregitopes are available for licensing for commercial and academic development across allergy, autoimmunity, transplantation, and tolerization of protein and gene therapies.[7] EVA Therapeutics would like to work with partners at any stage of development — from early target validation through IND-enabling studies. Contact us to discuss a partnership.

Note: all data described above are preclinical. Tregitope-based therapies have not been evaluated in human clinical trials.

References

De Groot AS, Moise L, McMurry JA, et al. Activation of natural regulatory T cells by IgG Fc-derived peptide “Tregitopes.” Blood. 2008;112(8):3303–3311. pmc.ncbi.nlm.nih.gov/articles/PMC2569179
Dembele M, Tao S, Massoud AH, Miah SMS, Lelias S, De Groot AS, Mazer BD. Tregitopes improve asthma by promoting highly suppressive and antigen-specific Tregs. Front Immunol. 2021;12:634509. pmc.ncbi.nlm.nih.gov/articles/PMC8089381
Cousens LP, Najafian N, Mingozzi F, et al. In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity. J Clin Immunol. 2013;33(Suppl 1):S43–S49. pmc.ncbi.nlm.nih.gov/articles/PMC3538121
Su Y, Rossi R, De Groot AS, Scott DW. Regulatory T cell epitopes (Tregitopes) in IgG induce tolerance in vivo and lack immunogenicity per se. J Leukoc Biol. 2013;94(2):377–383. pmc.ncbi.nlm.nih.gov/articles/PMC3714563
Cousens L, Najafian N, Martin WD, De Groot AS. Application of IgG-derived natural Treg epitopes (IgG Tregitopes) to antigen-specific tolerance induction in a murine model of type 1 diabetes. J Diabetes Res. 2013;2013:621693. pmc.ncbi.nlm.nih.gov/articles/PMC3655598
Sookrung N, Tungtrongchitr A, Chaicumpa W, et al. Tregitope-linked refined allergen vaccines for immunotherapy in cockroach allergy. Sci Rep. 2018;8:15402. doi.org/10.1038/s41598-018-33680-9
EpiVax demonstrates antigen-specific tolerance induction in allergy with Tregitopes, results published in Frontiers in Immunology. Press release, April 27, 2021. kyodonewsprwire.jp/release/202104274242