Anti-KIT antibodies and uses thereof
Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-mediated disorder or disease and methods of diagnosing a KIT-mediated disorder or disease using the antibodies described herein.
1. A method for treating or managing rheumatoid arthritis, inflammatory bowel disease, asthma, allergic inflammation, a gastrointestinal disorder or mastocytosis, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof, which immunospecifically binds to human KIT and comprises:
(i) a variable light (“VL”) chain region comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively; and
(ii) a variable heavy (“VH”) chain region comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25, respectively.
2. The method of claim 1 , wherein the method further comprises administering a second therapeutic agent.
3. The method of claim 2 , wherein the second therapeutic agent is a chemotherapeutic agent, tyrosine kinase inhibitor, an antibody, or a cytokine.
4. The method of claim 3 , wherein the tyrosine kinase inhibitor is imatinib mesylate or SU11248.
5. The method of claim 1 , wherein the antibody is a monoclonal antibody.
6. The method of claim 1 , wherein the antibody is a humanized antibody.
7. The method of claim 1 , wherein the antibody is a humanized monoclonal antibody.
8. The method of claim 1 , wherein the antibody comprises an Fc region of a human IgG1 or IgG4 antibody.
9. The method of claim 1 , wherein the antibody further comprises a human heavy chain constant region.
10. The method of claim 9 , wherein the human heavy chain constant region is a human gamma heavy chain constant region.
11. The method of claim 9 , wherein the human heavy chain constant region is an IgG1 or IgG4 human heavy chain constant region.
12. The method of claim 1 , wherein the antibody further comprises a human light chain constant region.
13. The method of claim 12 , wherein the human light chain constant region is a human kappa light chain constant region.
14. The method of claim 1 , wherein the antibody or antigen-binding fragment is linked to an agent.
15. The method of claim 1 , wherein the method is for treating or managing rheumatoid arthritis and the subject is in need of treatment or management of rheumatoid arthritis.
16. The method of claim 1 , wherein the method is for treating or managing inflammatory bowel disease and the subject is in need of treatment or management of inflammatory bowel disease.
17. The method of claim 1 , wherein the method is for treating or managing asthma and the subject is in need of treatment or management of asthma.
18. The method of claim 1 , wherein the method is for treating or managing allergic inflammation and the subject is in need of treatment or management of allergic inflammation.
19. The method of claim 1 , wherein the method is for treating or managing a gastrointestinal disorder and the subject is in need of treatment or management of gastrointestinal disorder.
20. The method of claim 1 , wherein the method is for treating or managing mastocytosis and the subject is in need of treatment or management of mastocytosis.