Regulatory T cell epitopes, compositions and uses thereof

Inventors

De Groot, Anne • Martin, William • Rivera, Daniel S.

Assignees

Epivax Inc

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 T-cell epitope compositions comprising one or more isolated T-cell epitope polypeptides derived from common human proteins. The compositions identify specific epitope polypeptides, including epitope polypeptides with amino acid sequences corresponding to defined SEQ ID NOS, and use epitope prediction and cluster tools to identify T-cell epitope clusters associated with binding to common HLA class II molecules.

The invention addresses inducing immune suppression by engaging regulatory T cells that already exist in a subject, including pre-existing natural regulatory T cells (CD4+CD25+FOXP3), through administration of a therapeutically effective amount of the T-cell epitope composition. The compositions activate natural regulatory T cells and thereby suppress immune responses, including suppression of co-administered antigen/therapeutics and reduced allergen responses.

The invention further describes associated immunological functions of the induced regulatory T-cell activity, including increased IL-10, TGF-β, TNF-α, and MCP-1, and decreased effector cytokines such as IFN-γ, IL-4, and IL-5, together with reduced proliferation. It also describes pharmaceutical and biological forms of Tregitopes, including nucleic acid, vector, and cell forms, for treatment or prevention of conditions for which immune modulation is desired.

Claims Coverage

The independent claim recites a method of inducing regulatory T-cells to suppress an immune response by administering a therapeutically effective amount of a T-cell epitope composition containing isolated T-cell epitope polypeptides, with at least one polypeptide consisting of the amino acid sequence of SEQ ID NO: 12. The claim set includes 7 inventive features, with dependent claims adding defined epitope sequences, antigens and/or allergens, and further narrowing suppression by natural regulatory T-cells, B-cell response, and effector T-cell cytokine secretion.

Across the independent claim and its dependents, the claimed coverage centers on administering a therapeutically effective T-cell epitope composition containing isolated T-cell epitope polypeptides, anchored by SEQ ID NO: 12, with additional defined epitope sequences and optional inclusion of antigens and/or allergens. The claim set further specifies that suppression is mediated by natural regulatory T-cells and can target B-cell responses and effector T-cell cytokine secretion.

Stated Advantages

Documented Applications