B7 family member zB7H6 and related compositions and methods
Disclosed is a newly identified B7 family member, zB7H6, which functions as a counter-receptor for the NK cell triggering receptor, NKp30. Methods and compositions for modulating NKp30-mediated NK cell activity based on the interaction of zB7H6 with NKp30, as well as related screening methods, are also disclosed. Further disclosed are anti-zB7H6 antibodies as well as antibody-drug conjugates comprising an anti-zB7H6 antibody conjugated to a therapeutic agent, including methods for using such antibodies and antibody-drug conjugates to exert therapeutic effects against zB7H6-expressing cells.
1. A method of screening for an antagonist of the interaction of zB7H6 with NKp30 comprising:
(a) contacting an agent with a zB7H6 polypeptide comprising residues 25-266 of SEQ ID NO: 2 in the presence of an NKp30 polypeptide comprising the extracellular domain of NKp30;
(b) detecting a measure of the interaction of the zB7H6 polypeptide with the NKp30 polypeptide; and
(c) determining whether the level of the zB7H6/NKp30 interaction measured in step (b) is significantly less relative to the level of interaction measured for control zB7H6 and NKp30 polypeptides in the absence of the agent, wherein
if the level of zB7H6/NKp30 interaction measured in step (b) is significantly less relative to the level of interaction measured for control zB7H6 and NKp30 polypeptides in the absence of the agent, then the agent is identified as an antagonist of the interaction of zB7H6 with NKp30.
2. The method of claim 1 wherein the agent is an antibody, single chain antibody, or Fv fragment, that specifically binds to zB7H6.
3. The method of claim 1 wherein the agent is a small molecule.
4. The method of claim 1 wherein at least one of the zB7H6 polypeptide and the NKp30 polypeptide is expressed on a cell.
5. The method of claim 1 wherein the measurement of interaction at step b is by detection of binding of the zB7H6 polypeptide to the NKp30 polypeptide.
6. The method of claim 1 wherein the measurement of interaction at step b is by detection of the ability of at least one of the zB7H6 polypeptide and the NKp30 polypeptide to trigger cellular activity mediated by the other.