| abstract |
Provided herein are multispecific immunomodulatory antigen-binding constructs (MIACs) and compositions comprising the constructs. Also provided are methods of using the constructs and methods of making the constructs. Described herein is a multispecific immunomodulatory antigen-binding construct (MIAC) polypeptide, comprising: an antigen-binding module I (ABMI) that binds specifically to an antigen expressed by a cancer cell; an antigen-binding module 2 (ABM2) that binds specifically to an activating receptor expressed by an effector immune cell, wherein binding of ABM2 to the activating receptor agonizes the activating receptor; and an antigen-binding module 3 (ABM3) that binds specifically to an inhibitory receptor expressed by the effector immune cell, wherein the binding of ABM3 to the inhibitory receptor antagonizes the inhibitory receptor, wherein ABMI, ABM2, and ABM3 are operably linked to each other, and optionally wherein each antigen binding module is capable of binding its respective antigen or receptor at the same time as each of the other antigen binding modules is bound to its respective antigen or receptor. |