Regulatory T cell epitopes
Inventors
Martin, William • Rosenberg, Amy S.
Assignees
United States, REPRESENTED BY SECRETARY Department Of Health And Human Services Food And Drug Administration AS • Epivax Inc • US Department of Health and Human Services
Publication Number
US-11441122-B2
Publication Date
2022-09-13
Expiration Date
2038-10-05
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Abstract
The present is directed to compositions comprising regulatory T cell epitopes, wherein said epitopes comprise a polypeptide comprising at least a portion of SEQ NOS: 1-14, fragments and/or variants thereof, as well as methods of producing and using the same.
Core Innovation
The invention relates to novel regulatory T cell epitopes termed “Tregitopes” and compositions comprising these epitopes. These Tregitopes are polypeptides comprising, consisting of, or consisting essentially of one or more amino acid sequences listed as SEQ ID NOS: 1-14. The compositions can include isolated, synthetic, or recombinant polypeptides; nucleic acids encoding the polypeptides; expression constructs; chimeric or fusion polypeptides; and pharmaceutical formulations. Methods for producing and using these compositions are also described.
The problem addressed is the need for less aggressive and more targeted methods for inducing immune tolerance that avoid the drawbacks of broad-based immune depleting therapies, which compromise the immune system globally and increase vulnerability to infections and other diseases. The disclosed Tregitopes aim to activate naturally occurring regulatory T cells (TRegs), including natural and adaptive TRegs, in an antigen-specific manner to suppress unwanted immune responses, such as those against self or foreign antigens, therapeutic proteins, and transplants.
Claims Coverage
The claims focus on methods of inducing regulatory T-cells using compositions containing specific T-cell epitope polypeptides to suppress immune responses. There are multiple inventive features centered on specific sequences, additional epitopes, composition combinations, and effects on immune cell responses.
Method of inducing regulatory T-cells with specific epitope polypeptides
A method comprising administration to a subject of a therapeutically effective amount of a T-cell epitope composition including one or more isolated T-cell epitope polypeptides where at least one consists of the amino acid sequence SEQ ID NO: 1.
Inclusion of additional epitope polypeptides
The T-cell epitope composition further comprises one or more isolated T-cell epitope polypeptides selected from the group consisting of SEQ ID NOS: 2-14.
Combination with antigens and allergens
The T-cell epitope composition also includes an effective amount of one or more antigens and/or allergens.
Immune suppression mediated by natural regulatory T cells
The immune suppressive effect achieved by the composition is mediated through natural regulatory T cells.
Immune suppression mediated by adaptive regulatory T-cells
The immune suppressive effect achieved by the composition is mediated through adaptive regulatory T-cells.
Suppression of effector T-cell responses
The T-cell epitope composition suppresses effector T-cell responses.
Suppression of effector T-cell cytokine secretion
The T-cell epitope composition suppresses cytokine secretion by effector T-cells.
Suppression of helper T-cell responses
The T-cell epitope composition suppresses helper T-cell responses.
Suppression of B-cell responses
The T-cell epitope composition suppresses B-cell responses.
The claims cover methods of immunomodulation by administering T-cell epitope compositions including specific polypeptides, especially SEQ ID NO: 1, alone or combined with other epitopes or antigens/allergens, to induce regulatory T-cells mediating suppression of diverse immune effectors.
Stated Advantages
Treatment is highly antigen specific by expanding and stimulating naturally occurring regulatory T cells in an antigen-specific manner.
The treatment regimen is more efficient and less expensive compared to current therapies requiring prolonged, high-dose factor VIII infusions.
Provides a second line of defense when high-dose factor VIII treatment fails to induce immune tolerance in patients.
Documented Applications
Suppressing unwanted immune responses including autoimmune diseases such as type 1 diabetes, multiple sclerosis, lupus, and rheumatoid arthritis.
Treating transplant-related disorders including graft versus host disease (GVHD) and host versus graft disease.
Managing allergic reactions and asthma through induction of allergen-specific tolerance.
Reducing immune rejection of biologic medicines such as monoclonal antibodies and replacement proteins including coagulation Factor VIII supplements used in Hemophilia A.
Treatment or prevention of viral, bacterial, or parasitic infections.
Ex vivo expansion and stimulation of regulatory T cells for therapeutic use.
Use as tolerizing agents for immunogenic protein therapeutics to reduce adverse immune responses.
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