Anti-B7-H3 antibody and use thereof
Provided is an anti-B7-H3 antibody specifically recognizing a B7-H3, which can be usefully as a cancer therapeutic agent, as having an inhibitory activity of an immune checkpoint which induces antibody-dependent cell-mediated cytotoxicity and T cell activation inhibited by B7-H3. In particular, the antibody having the inhibitory activity of an immune checkpoint can be used in combination with other immunoantibody therapeutic agents. In addition, it can be usefully used for cancer targeting treatment including detection of various cancers expressing B7-H3 through specific binding to B7-H3, and drug delivery to specific cancer, etc.
1. An isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment,
wherein the antibody or antigen-binding fragment comprises (i) heavy chain complementarity determining regions of CDRH1, CDRH2 and CDRH3, and (ii) light chain complementarity determining regions of CDRL1, CDRL2 and CDRL3, and wherein,
(a) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 1, 5, and 10, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 15, 20 and 25, respectively;
(b) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 2, 6, and 11, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 16, 21 and 26, respectively;
(c) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 3, 7, and 12, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 17, 22 and 27, respectively;
(d) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 1, 8, and 13, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 18, 23 and 28, respectively;
(e) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 4, 9, and 14, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 19, 24 and 29, respectively
(f) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 3, 68, and 12, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 17, 22, and 27, respectively; or
(g) the CDRH1, CDRH2 and CDRH3 are SEQ ID NOs: 3, 68, and 12, respectively, and the CDRL1, CDRL2, and CDRL3 are SEQ ID NOs: 17, 69, and 27, respectively.
2. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 ,
comprising a combination of a heavy chain variable region and a light chain variable region, represented by the following sequence:
SEQ ID NOs: 30 and 35; SEQ ID NOs: 31 and 36; SEQ ID NOs: 32 and 37; SEQ ID NOs: 33 and 38; SEQ ID NOs: 34 and 39; SEQ ID NOs: 70 and 37; or SEQ ID NOs: 70 and 71.
3. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 ,
comprising a combination of a heavy chain and a light chain, represented by the following sequence:
SEQ ID NOs: 50 and 55; SEQ ID NOs: 51 and 56; SEQ ID NOs: 52 and 57; SEQ ID NOs: 53 and 58; SEQ ID NOs: 54 and 59; SEQ ID NOs: 74 and 57; or SEQ ID NOs: 74 and 75.
4. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 , wherein the antibody or antigen-binding fragment is a monoclonal antibody.
5. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 , wherein the monoclonal antibody is an IgG1, IgG2, IgG3 or IgG4 type.
6. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 , wherein the B7-H3 is B7-H3 of human, mouse or monkey.
7. The isolated antibody specifically recognizing B7-H3 or its antigen-binding fragment according to claim 1 , wherein the antibody or antigen-binding fragment is Fab, Fab′, F(ab′) 2 , scFab, Fv, dsFv, scFV, scFV-Fc, minibody, diabody, scAb, bivalent antibody or multivalent antibody.
8. An isolated polynucleotide encoding the antibody or its antigen-binding fragment according to claim 1 .
9. A vector comprising a polynucleotide encoding the antibody or its antigen-binding fragment according to claim 1 .
10. A cell line transformed with a vector comprising the polynucleotide encoding the antibody or its antigen-binding fragment according to claim 1 .
11. A pharmaceutical composition, comprising the antibody or its antigen-binding fragment according to claim 1 and a pharmaceutically acceptable excipient.
12. A method for treating a disease related to overexpression of B7-H3, comprising a step of administering the antibody or its antigen-binding fragment according to claim 1 and a pharmaceutically acceptable excipient, to a subject in need thereof, wherein the disease related to overexpression of B7-H3 is cancer.
13. A method for diagnosing a disease related to overexpression of B7-H3, comprising
a step of contacting the antibody or its antigen-binding fragment according to claim 1 with a biological sample, and
a step of determining the biological sample or a patient from who the biological sample obtained as having a disease related to overexpression of B7-H3, when B7-H3 is present or the concentration of B7-H3 is increased in the biological sample as compared to a control group contacted with the antibody or its antigen-binding fragment,
wherein the disease related to overexpression of B7-H3 is cancer.
14. The method according to claim 12 , wherein the method comprises reactivating an activity of a T cell inhibited by a B7-H3 immune checkpoint.