Suppressing IgE-mediated allergy by desensitization with monovalent anti-FCeRIa monoclonal antibody
A monovalent monoclonal antibody is provided, the antibody including one light chain, one heavy chain, and one truncated heavy chain, wherein the truncated heavy chain lacks a variable domain and a CH1 domain and wherein the antibody specifically binds an epitope of FcεRIα. Also provided are methods of desensitizing a subject to an allergen, methods of treating an allergy, and methods of preventing an allergic reaction in a subject having an allergy.
1 . A monovalent monoclonal antibody (mAb) comprising one light chain, one heavy chain comprising SEO ID NO: 12, wherein the heavy chain comprises a variable region comprising SEQ ID NO: 4 and a constant region comprising an E356K mutation (corresponding to amino acid residue 378 of SEQ ID NO.12) and a D399K mutation (corresponding to amino acid residue 421 of SEQ ID NO:12), and one truncated heavy chain comprising SEO ID NO: 13, wherein the mAB specifically binds an epitope of FcεRIα, and wherein the mAb comprises complimentary determining regions having SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7; SEQ ID NO: 8; SEQ ID NO: 9; and SEQ ID NO: 10.
2 . The monovalent mAb according to claim 1 , wherein the mAb does not compete with IgE for binding to FcεRIα.
3 . The monovalent mAb according to claim 1 , wherein the epitope of FcεRIα is the same epitope bound by IE7.
4 . The monovalent mAb according to claim 1 , wherein the mAb binds to human FcεRIα.
5 . The monovalent mAb according to claim 1 , wherein the light chain is a kappa chain.
6 . The monovalent mAb according to claim 1 , wherein the heavy chain is a gamma chain.
7 . The monovalent mAb according to claim 6 , wherein the heavy chain is gamma subclass 4.
8 . The monovalent mAb according to claim 1 , wherein the light chain comprises a variable region encoded by SEQ ID NO: 1.
9 . The monovalent mAb according to claim 1 , wherein the heavy chain comprises a variable region encoded by SEQ ID NO: 2.
10 . A pharmaceutical composition comprising the monovalent mAb according to claim 1 .
11 . A polynucleotide or a combination of polynucleotides encoding the monovalent mAb according to claim 1 .
12 . A vector comprising the polynucleotide or combination of polynucleotides according to claim 11 .
13 . A host cell comprising the polynucleotide or combination of polynucleotides according to claim 11 .