Antibodies specific to folate receptor alpha
Antibodies specific to folate receptor alpha (a.k.a. folate receptor 1 or FOLR1) and uses thereof for therapeutic and diagnostic purposes. Also provided herein are chimeric antigen receptors (CARs) comprising an extracellular antigen-binding fragment that binds FOLR1 and immune cells expressing such.
1. An isolated antibody that binds to FOLR1, wherein the isolated antibody comprises a heavy chain variable region (V H ) comprising a heavy chain complementary determining region 1 (HC CDR1) of the amino acid sequence of SEQ ID NO: 8, a HC CDR2 of the amino acid sequence of SEQ ID NO: 11, and a HC CDR3 of the amino acid sequence of SEQ ID NO: 14, and a light chain variable region (V L ) comprising a light chain CDR1 (LC CDR1) of the amino acid sequence of SEQ ID NO: 5, a LC CDR2 of the amino acid sequence WAS, and a LC CDR3 of the amino acid sequence of SEQ ID NO: 19.
2. The isolated antibody of claim 1 , wherein the V H is at least 85% identical to a V H of the amino acid sequence of SEQ ID NO: 21, and/or wherein the V L is at least 85% identical to a V L of the amino acid sequence of SEQ ID NO: 22.
3. The isolated antibody of claim 2 , wherein the V H comprises the amino acid sequence of SEQ ID NO: 21 and/or the V L comprises the amino acid sequence of SEQ ID NO: 22.
4. The isolated antibody of claim 1 , wherein the isolated antibody is an IgG molecule.
5. The isolated antibody of claim 4 , wherein the isolated antibody is a human antibody, a humanized antibody, or a chimeric antibody.
6. The isolated antibody of claim 1 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof, or a single-chain antibody.
7. A nucleic acid or set of nucleic acids, which collectively encodes an anti-FOLR1 antibody of claim 1 .
8. A vector or set of vectors comprising the nucleic acid(s) of claim 7 .
9. A host cell comprising the vector or vector set of claim 8 .
10. An antibody-drug conjugate (ADC) comprising:
i. an antibody of claim 1 ; and
ii. at least one therapeutic agent;
wherein the antibody is covalently conjugated to the at least one therapeutic agent.
11. A chimeric antigen receptor comprising:
(i) an extracellular domain comprising the isolated antibody of claim 1 ,
(ii) a transmembrane domain, and
(iii) one or more intracellular stimulatory domains.
12. The chimeric antigen receptor of claim 11 , wherein the V H is at least 85% identical to a V H of the amino acid sequence of SEQ ID NO: 21, and/or wherein the V L is at least 85% identical to a V L of the amino acid sequence of SEQ ID NO: 22.
13. The chimeric antigen receptor of claim 11 , wherein the V H comprises the amino acid sequence of SEQ ID NO: 21 and/or the V L comprises the amino acid sequence of SEQ ID NO: 22.
14. The chimeric antigen receptor of claim 11 , wherein the isolated antibody is a single chain antibody (scFv).
15. The chimeric antigen receptor of claim 11 , wherein the transmembrane domain comprises a transmembrane domain derived from a CD28, or CD8 receptor.
16. The chimeric antigen receptor of claim 11 , wherein (iii) comprises a signaling domain from CD3ζ.
17. The chimeric antigen receptor of claim 11 , wherein (iii) comprises a co-stimulatory signaling domain.
18. A pharmaceutical composition comprising (i) an antibody of claim 1 ; and (ii) a pharmaceutically acceptable carrier.
19. A method of reducing the number of FOLR1+ cells, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 18 .
20. A method of detecting presence of FOLR1+ cells, the method comprising:
i. contacting a sample suspected of having FOLR1+ cells with an antibody of claim 1 , wherein the antibody is conjugated with a labeling agent; and
ii. detecting presence FOLR1+ cells in the sample based on binding of the antibody to cells in the sample.