Anti-folate receptor 1 antibodies and uses thereof

1. An isolated monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, having the polypeptide sequence of:

(a) SEQ ID NOs: 29, 30, 31, 53, 54 and 55, respectively, or SEQ ID NOs: 77, 78, 79, 101, 102, and 103, respectively;

(b) SEQ ID NOs: 20, 21, 22, 44, 45 and 46, respectively, or SEQ ID NOs: 68, 69, 70, 92, 93, and 94, respectively; or

(c) SEQ ID NOs: 35, 36, 37, 59, 60 and 61, respectively, or SEQ ID NOs: 83, 84, 85, 107, 108, and 109, respectively;

wherein the antibody or antigen-binding fragment thereof specifically binds FOLR1.

2. The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , comprising a heavy chain variable region having a polypeptide sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 120, 9, 3, 13, 113, 114, 115, 116, or 119, or a light chain variable region having a polypeptide sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 122, 10, 4, 14, 117, 118, 121, or 123.

3. The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , comprising:

(a) a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 120, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 122;

(b) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:9, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 10;

(c) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:3, and a light chain variable region having the polypeptide sequence of SEQ ID NO:4;

(d) a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 13, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 14;

(e) a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 113, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 117;

(f) a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 113, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 118;

(g) a heavy chain variable region having the polypeptide sequence of SEQ ID NO: 114, and a light chain variable region having the polypeptide sequence of SEQ ID NO: 117;

(h) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:114, and a light chain variable region having the polypeptide sequence of SEQ ID NO:118;

(i) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:115, and a light chain variable region having the polypeptide sequence of SEQ ID NO:117;

(j) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:115, and a light chain variable region having the polypeptide sequence of SEQ ID NO:118;

(k) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:116, and a light chain variable region having the polypeptide sequence of SEQ ID NO:117;

(l) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:116, and a light chain variable region having the polypeptide sequence of SEQ ID NO:118;

(m) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:119, and a light chain variable region having the polypeptide sequence of SEQ ID NO:121;

(n) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:119, and a light chain variable region having the polypeptide sequence of SEQ ID NO:122;

(o) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:119, and a light chain variable region having the polypeptide sequence of SEQ ID NO:123;

(p) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:120, and a light chain variable region having the polypeptide sequence of SEQ ID NO:121; or

(q) a heavy chain variable region having the polypeptide sequence of SEQ ID NO:120, and a light chain variable region having the polypeptide sequence of SEQ ID NO:123.

4. The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is chimeric or humanized.

5. The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof is capable of binding FOLR1 and inducing effector-mediated tumor cell lysis.

6. A pharmaceutical composition, comprising the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

7. A method of treating cancer or targeting FOLR1 on a cancer cell surface in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 6 .

8. A method of producing a pharmaceutical composition comprising the monoclonal antibody or antigen-binding fragment of claim 1 , comprising combining the monoclonal antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

9. A method of determining a level of FOLR1 in a subject, the method comprising:

(a) obtaining a sample from the subject;

(b) contacting the sample with the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 ; and

(c) determining a level of FOLR1 in the subject.

10. The method of claim 9 , wherein the sample is a tissue sample or a blood sample.

11. The method of claim 10 , wherein the tissue sample is a cancer tissue sample.

12. An isolated bi specific antibody or antigen-binding fragment thereof comprising the monoclonal antibody or antigen-binding fragment thereof of claim 1 .

13. A pharmaceutical composition comprising the isolated bispecific antibody or antigen-binding fragment thereof of claim 12 and a pharmaceutically acceptable carrier.