Antibody and antigen-binding fragment compositions targeting cell surface antigens in tumors and methods of use thereof
Described herein is an isolated antibody or antigen-binding fragment including a heavy chain variable region including three heavy chain complementary determining regions (HCDRs), wherein the sequence of HCDR1 is GYRLSELS (SEQ ID NO: 1), the sequence of HCDR2 is ISGWDGNT (SEQ ID NO: 2), and the sequence of HCDR3 is ARASGYNY(SEQ ID NO: 3), wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90, specifically HSP90 beta. Also included are detection and therapeutic methods using the isolated antibodies or antigen-binding fragments.
1. An isolated antibody or antigen-binding fragment comprising a heavy chain variable region comprising three heavy chain complementary determining regions (HCDRs), wherein the sequence of HCDR1 is GYRLSELS (SEQ ID NO: 1), the sequence of HCDR2 is ISGWDGNT (SEQ ID NO: 2), and the sequence of HCDR3 is ARASGYNY(SEQ ID NO: 3), wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90.
2. The isolated antibody or antigen-binding fragment of claim 1 , wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90beta.
3. The isolated antibody or antigen-binding fragment of claim 1 , comprising a heavy chain region having at least 95% sequence identity with SEQ ID NO: 4.
4. The isolated antibody or antigen-binding fragment of claim 3 , comprising a heavy chain region having SEQ ID NO: 4.
5. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody is a single chain antibody consisting of the heavy chain variable region as defined in claim 1 .
6. The isolated antibody or antigen-binding fragment of claim 5 , wherein the single chain antibody consists of a heavy chain region having at least 95% sequence identity with SEQ ID NO: 4.
7. The isolated antibody or antigen-binding fragment of claim 6 , wherein the single chain antibody consists of a heavy chain region having SEQ ID NO: 4.
8. The isolated antibody or antigen-binding fragment of claim 1 , further comprising an Fc region fused to the heavy chain variable region.
9. The isolated antibody or antigen-binding fragment of claim 8 , further comprising a light chain.
10. The isolated antibody or antigen-binding fragment of claim 9 , wherein the light chain comprises SEQ ID NO:5, SEQ ID NO: 6, SEQ ID NO: 7, or SEQ ID NO: 8.
11. The isolated antibody or antigen-binding fragment of claim 1 , further comprising an attached detectable moiety or therapeutic agent.
12. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.
13. A method of detecting the presence of HSP90 in a biological sample, the method comprising contacting the biological sample with the isolated antibody or antigen-binding fragment of claim 1 and detecting binding of the isolated antibody or antigen-binding fragment to HSP90, wherein binding indicates the presence of HSP90 in the sample.
14. The method of claim 13 , wherein the isolated antibody or antigen-binding fragment specifically binds human HSP90 beta.
15. The method of claim 13 , wherein detecting comprises performing an immunoassay.
16. The method of claim 15 , wherein the immunoassay is a Western blot, immunofluorescence assay, an enzymatic immunoassay, an enzyme-linked immunosorbent assay, immunohistochemistry, immunoprecipitation, immunoelectrophoresis, a dipstick, an assay strip radioimmunometric assay, a tissue microarray assay, or an immunoturbidimetric assay.
17. The method of claim 16 , wherein the immunofluorescence assay uses confocal microscopy detection.