Regulatory T cell epitopes, compositions and uses thereof
Inventors
De Groot, Anne • Martin, William • Rivera, Daniel S.
Assignees
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Publication Number
US-12016909-B2
Publication Date
2024-06-25
Expiration Date
Abstract
The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.
Core Innovation
The invention provides chimeric polypeptides comprising a first and a second polypeptide chain linked together, where the first polypeptide chain is a fragment of an immunoglobulin consisting of the amino acid sequence of SEQ ID NO: 12. The second polypeptide chain comprises a biologically active molecule that is not an immunoglobulin polypeptide, and the linked chains may be configured with the second polypeptide chain fused to the N-terminus or the C-terminus of the first polypeptide chain.
Additional embodiments include at least one isolated T-cell epitope polypeptide with amino acid sequences selected from specified SEQ ID sets, thereby defining T-cell epitope content within the overall chimeric polypeptide. Related discussion includes chimeric/fusion constructs involving FVIII-Tregitope and multi-Tregitope concepts.
The disclosed approach is directed to inducing regulatory T-cells to suppress immune response in a subject by administering a therapeutically effective amount of the chimeric polypeptide. The document further describes T-cell epitope compositions that bind common HLA class II and selectively activate pre-existing natural regulatory T cells (CD4+CD25+FOXP3), inducing regulatory cytokines such as IL-10 and TGF-β and suppressing effector T-cell responses.
Claims Coverage
The provided set includes two independent claims. Across them, the inventive coverage focuses on a chimeric polypeptide architecture combining an immunoglobulin fragment with a non-immunoglobulin biologically active molecule, and on using that chimeric polypeptide in a method to induce regulatory T-cells that suppress immune response, with optional fusion orientation and inclusion of defined T-cell epitope polypeptides.
Immunoglobulin fragment linked to non-immunoglobulin biologically active molecule
A chimeric polypeptide comprising a first and a second polypeptide chain linked together, wherein said first polypeptide chain is a fragment of an immunoglobulin consisting of the amino acid sequence of SEQ ID NO: 12, wherein the second polypeptide chain comprises a biologically active molecule, and wherein said biologically active molecule is not an immunoglobulin polypeptide.
Inducing regulatory t-cells to suppress immune response by administering the chimeric polypeptide
A method of inducing regulatory T-cells to suppress immune response in a subject comprising administrating to the subject a therapeutically effective amount of a chimeric polypeptide, wherein the chimeric polypeptide comprises a first and a second polypeptide chain linked together, wherein said first polypeptide chain is a fragment of an immunoglobulin consisting of the amino acid sequence of SEQ ID NO: 12, wherein the second polypeptide chain comprises a biologically active molecule, and wherein said biologically active molecule is not an immunoglobulin polypeptide.
Overall, the claim coverage centers on chimeric constructs that link an immunoglobulin fragment defined by SEQ ID NO: 12 to a second, non-immunoglobulin biologically active molecule, and on administering that construct to induce regulatory T-cells that suppress an immune response in a subject. Dependent claim refinements further specify fusion orientation and can require inclusion of isolated T-cell epitope polypeptides from defined SEQ ID sets.
Stated Advantages
Induces regulatory T-cells to suppress immune response in a subject.
Selectively activates pre-existing natural regulatory T cells (CD4+CD25+FOXP3).
Induces regulatory cytokines such as IL-10 and TGF-β.
Suppresses effector T-cell responses.
Documented Applications
Therapeutic use in autoimmunity, allergy, transplantation and graft-versus-host disease (GVHD), infections, and therapeutic protein immunogenicity, as described in the partial content.
Use of nucleic acids, vectors, and cells, as well as kits, and ex vivo/in vitro regulatory T-cell expansion or stimulation, as described in the partial content.
Use in connection with chimeric/fusion constructs including FVIII-Tregitope and multi-Tregitope concepts, as described in the partial content.
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