CD1a antibodies and uses thereof
Antibodies, and antigen-binding fragments thereof, that specifically bind to Cluster of Differentiation 1a (CD1a) are provided. Embodiments include uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.
1 . A method of inhibiting Cluster of Differentiation 1a (CD1a)-dependent T cell activation in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of an antibody, or antigen binding fragment thereof, that specifically binds to human CD 1a,
wherein the antibody comprises:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30,
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41,
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17,
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25,
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27,
thereby inhibiting CD1a-dependent T cell activation.
2 . The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises at least one of the following:
(i) a heavy chain variable region (VH) framework sequence obtained from a human germline VH sequence selected from the group consisting of IGHV1-2*02, IGHV1-3*01, IGHV1-46*01, IGHV1-69*01, IGHV1-69*02, IGHV1-8*01, IGHV3-7*01, IGHV3-13*01, IGHV3-23*01, IGHV3-23*04, IGHV3-30*01, IGHV3-30*18, IGHV5-10-1*01, IGHV5-10-1*04, and IGHV5-51*01;
(ii) a light chain variable region (VL) framework sequence obtained from a human germline VL sequence selected from the group consisting of IGKV1-12*01, IGKV1-13*02, IGKV1-33*01, IGKV1-39*01, IGKV1-5*01, IGKV3-11*01, IGKV3-15*01, IGKV3-20*01, IGKV3D-20*02, and IGKV4-1*01;
(iii) a heavy chain constant domain comprising an IgA, IgD, IgE, IgM, or IgG; and/or
(iv) a human Vκ or Vλ light chain constant domain.
3 . The method of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises:
(i) a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 28;
(ii) a HC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 54 and a LC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 24; or
(iii) the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
4 . The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises a VL comprising the sequence of SEQ ID NO:28 and a VH comprising the sequence of SEQ ID NO: 55.
5 . The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises a light chain comprising the amino acid sequence of SEQ ID NO: 24 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 54.
6 . The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, binds an epitope on CD 1a, wherein the epitope comprises Glu82 and/or His170, according to the numbering of SEQ ID NO: 1, and where the epitope:
(i) optionally further comprises Ile92 and/or Arg93, according to the numbering of SEQ ID NO: 1, and
(ii) optionally comprises at least one of the following amino acid residues: Glu78, Lys81, Thr85, Ile89, Arg93, Asp173, and Asn177, according to the numbering of SEQ ID NO: 1; and
(iii) optionally comprises at least one of the following residues: Leu86, Asn168, Ile174, His176, Asp181, and Arg185, according to the numbering of SEQ ID NO: 1; and
(iv) optionally comprises at least one of the following residues: Glu79, Leu83, Glu84, Arg88, Ile92, Gln169, Leu178, Ser180, and Thr182 according to the numbering of SEQ ID NO: 1; and
(v) optionally does not comprise Asn146 and/or Asn168 according to the numbering of SEQ ID NO: 1.
7 . The method of claim 1 , wherein the binding inhibits CD1a from binding a T cell receptor.
8 . The method of claim 1 , wherein the binding inhibits CD69 expression.
9 . The method of claim 1 , wherein the binding inhibits IL-2 production.
10 . The method of claim 1 , wherein the binding inhibits serum IgE levels.
11 . The method of claim 1 , wherein the binding inhibits antigen-specific IgE antibodies.
12 . The method of claim 1 , wherein the binding inhibits expression of a gene selected from the group consisting of: Thymic Stromal Lymphopoietin (TSLP), filaggrin (FLG), interleukin-33 (IL-33), C—C motif chemokine ligand 26 (CCL-26), IL-23p40, C—X—C chemokine ligand 1 (CXCL-1), and CCL-20.
13 . The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is comprised in a pharmaceutical composition with a pharmaceutically acceptable carrier or excipient.
14 . The method of claim 1 , wherein the therapeutically effective amount of the antibody, or antigen binding fragment thereof, is sufficient to inhibit CD1a-dependent T cell activation in the subject in need thereof.
15 . The method of claim 1 , wherein the subject in need thereof suffers from an inflammatory bowel disease.
16 . The method of claim 1 , wherein the subject in need thereof suffers from an inflammatory skin disease.
17 . The method of claim 1 , wherein the subject in need thereof suffers from atopic dermatitis.
18 . The method of claim 1 , wherein the subject in need thereof suffers from an allergy.
19 . The method of claim 1 , wherein the subject in need thereof suffers from: inflammatory bowel disease, allergies, allergic rhinitis, allergic conjunctivitis, vernal keratoconjunctivitis, a seasonal allergy, pet allergy, asthma, food allergy, peanut allergy, atopic dermatitis, contact dermatitis, chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis, bronchitis, chronic obstructive pulmonary disease (COPD), viral exacerbations of respiratory disease, viral infection in children and adults, respiratory syncytial virus RSV, rhinovirus, influenza, urticarias, eosinophilic esophagitis, chronic fibrosis, liver fibrosis, non-alcoholic steatohepatitis (NASH), chronic kidney disease, idiopathic pulmonary fibrosis (IPF), scleroderma, systemic sclerosis, acute kidney injury, sepsis, pancreatitis, type 1 diabetes, graft-versus-host disease (GVHD), tissue transplant, Alzheimer's, rheumatoid arthritis, irritable bowel syndrome (IBS), Crohn's disease, ulcerative colitis, multiple sclerosis, psoriasis, celiac disease, or Raynaud's disease.