Proteinaceous compound for generating specific cytotoxic t-cell effect

Patent metadata

Field	Value
Publication number	US-2025059254-A1
Application number	US-202318724341-A
Country	US
Kind code	A1
Filing date	Jan 3, 2023
Priority date	Jan 3, 2022
Publication date	Feb 20, 2025
Grant date	—

Abstract

The present invention relates to a proteinaceous compound comprising a first binding moiety, such as an antibody or fragment thereof, having affinity for a target of interest, and a pMHC comprising an MHC molecule, such as an HLA molecule, presenting an antigenic peptide, wherein the presented antigenic peptide has affinity for CD8+ T-cells induced by the antigenic peptide, such as induced by vaccination. The present invention further relates to the proteinaceous compound for use as a medicament. Also, the present invention relates to the proteinaceous compound for treatment of cancer and for treating of a subject infected with a pathogen.

First claim

1 . A proteinaceous compound comprising:
a) a first binding moiety, having affinity for a target of interest, and b) a pMHC comprising an MHC molecule, presenting an antigenic peptide, wherein the presented antigenic peptide has affinity for CD8+ T-cells induced by the antigenic peptide, wherein β2-microglobulin is non-covalently associated.

2 - 32 . (canceled)

33 . The proteinaceous compound according to claim 1 , wherein a first subunit comprises said antigenic peptide of the pMHC, the β2-microglobulin and said first binding moiety.

34 . The proteinaceous compound according to claim 1 , wherein the antigenic peptide is derived from a virus.

35 . The proteinaceous compound according to claim 1 , wherein the antigenic peptide is derived from Yellow Fever Virus (YFV), measles, rubella, varicella or smallpox.

36 . The proteinaceous compound according to claim 1 , wherein the antigenic peptide comprises or consists of an epitope selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15.

37 . The proteinaceous compound according to claim 1 , comprising a second binding moiety having affinity for a target of interest.

38 . The proteinaceous compound according to claim 1 , wherein a first subunit comprises said antigenic peptide of the pMHC, the β2-microglobulin and said first binding moiety; and a second subunit comprises the MHC molecule without the β2-microglobulin and a second binding moiety, having affinity for a target of interest.

39 . The proteinaceous compound according to claim 1 , wherein a first subunit comprises said antigenic peptide of the pMHC, the β2-microglobulin and said first binding moiety; and a second subunit comprises the MHC molecule without the β2-microglobulin and a second binding moiety, having affinity for a target of interest wherein the first binding moiety and second binding moiety have affinity for different targets of interest.

40 . The proteinaceous compound according to claim 1 , wherein a first subunit comprises said antigenic peptide of the pMHC, the β2-microglobulin and said first binding moiety; and a second subunit comprises the MHC molecule without the β2-microglobulin and a second binding moiety, having affinity for a target of interest said first subunit and said second subunit being linked via a heterodimerization domain.

41 . The proteinaceous compound according to claim 1 , wherein a first subunit comprises said antigenic peptide of the pMHC, the β2-microglobulin and said first binding moiety; and a second subunit comprises the MHC molecule without the β2-microglobulin and a second binding moiety, having affinity for a target of interest said first subunit and said second subunit being linked via a heterodimerization domain selected from the group consisting of a Knob-into-Hole system, c-jun transcription factor derived dimerization domains, and leucine zipper dimerization domains.

42 . The proteinaceous compound according to claim 1 , wherein the binding moiety is selected from the group consisting of polyclonal antibody, a monoclonal antibody, an antibody wherein the heavy chain and the light chain are connected by a flexible linker, an Fv molecule, an antigen binding fragment, a Fab fragment, a Fab′ fragment, a F(ab′)2 molecule, a fully human antibody, a humanized antibody, a chimeric antibody, scFv (single-chain variable fragment) and a single-domain antibody (sdAb) (nanobody or diabody), preferably a scFv (single-chain variable fragment) and a single-domain antibody (sdAb) (nanobody or diabody).

43 . The proteinaceous compound according to claim 1 , wherein the binding moiety having affinity for a target of interest, has affinity for
an intracellular pathogen; or a cancer cell surface protein.

44 . The proteinaceous compound according to claim 1 , wherein the binding moiety having affinity for a target of interest, has affinity for
immunodeficiency virus (HIV), viral hepatitis or human T-cell lymphotropic virus type 1 (HTLV); or CD19, CD4, CD20, GD2, PSMA, or Mesothelin.

45 . The proteinaceous compound according to claim 1 , wherein the proteinaceous compound is in a composition.

46 . A method of treating a subject infected with an intracellular pathogen or suffering from cancer, the method comprising administering the proteinaceous compound according to claim 1 , wherein the subject has previously received a vaccine for inducing CD8+ T-cells directed against the antigenic peptide;
wherein the binding moiety, having affinity for a target of interest, has affinity for an epitope of the pathogen causing the disease or a cell surface marker of the cancer.

47 . A nucleic acid encoding a proteinaceous compound comprising:
a) a first binding moiety, having affinity for a target of interest, and b) a pMHC comprising an MHC molecule, presenting an antigenic peptide, wherein the presented antigenic peptide has affinity for CD8+ T-cells induced by the antigenic peptide, wherein β2-microglobulin is non-covalently associated.

48 . The nucleic acid according to claim 47 , wherein the nucleic acid is comprised in a vector.

49 . The nucleic acid according to claim 47 , wherein the nucleic acid is in the form of a plasmid.

50 . The nucleic acid according to claim 47 , wherein the nucleic acid is comprised a cell.

51 . The nucleic acid according to claim 47 , wherein the nucleic acid is comprised in a mammalian cell.

Assignees

• Univ Aarhus
• Region Midtjylland

Inventors

• Tolstrup Martin
• Schleimann Mariane Høgsbjerg
• Konrad Christina Valbirk
• Gunst Jesper Damsgaard

Classifications

• C07K16/1145 Primary

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title