JAML specific binding agents, antibodies, and uses related thereto
Certain embodiments of the disclosure relate to targeted binding agents that specifically bind to JAM-like protein and therein inhibit epithelial damage. Although it is not intended that embodiments of the disclosure be limited by any particular mechanism, it is believed that a possible mechanism by which this can be achieved may include, but are not limited to, either inhibition of binding of JAML to the CAR, inhibition of JAML induced CAR signaling, or increased clearance of JAML from the body of a subject, therein reducing the effective concentration of soluble JAML. In certain embodiment, the specific binding agent is a fully human antibody or chimera that specifically binds to human JAML, such as the JAML D1, and prevents JAML binding to CAR. Certain embodiments of the disclosure contemplate antibodies comprising human IgG type, e.g., IgG1, IgG2, IgG3, and IgG4.
1. A chimeric JAML antibody that substantially prevents human JAML from binding CAR having CDR1, CDR2, and CDR3 heavy chain respective sequences of:
(SEQ ID NO: 27) DYE,
(SEQ ID NO: 37) PGSGGT,
(SEQ ID NO: 35) GSSYN; and
having CDR1, CDR2, and CDR3 light chain respective sequences of:
(SEQ ID NO: 64) RASEN
(SEQ ID NO: 60) NANSLEDGVP; and
(SEQ ID NO: 12) YFCEQTYDVPLTFGAGT,
wherein the antibody does not substantially bind to JAMA or JAMC.
2. The chimeric JAML antibody of claim 1 , wherein the heavy chain comprises (SEQ ID NO: 19) DVQLVESGAELVRPGASKLSCKALAYTFTDYEMHWVKQTPVHGLEWIGIIHPGSGGTV YNQKFKGKATLTADKSSSTAYMELSSLTSEDSTVYYCTRRRYYGSSYNWYFDVWGAG N.
3. The chimeric JAML antibody of claim 1 , wherein the light chain comprises (SEQ ID NO:22) VLTQSPASLAASVGETVTITCRASENIYYSLAWYQQKQGKSPQLLIYNANSLEDGVPSRF SGSGSGTQYSLKINSMQPEDTATYFCEQTYDVPLTFGAGTKLEL.
4. A hybridoma which produces DW100 monoclonal antibodies deposited in the American Type Culture Collection (ATCC) with a Patent Deposit Designation of PTA-13051.