Tumor cell ligands for activating NK receptors and antibody Fc via CD16, plus CAR-defined tumor antigens (NK/CD16/CAR-TAA)

This target profile describes a composite of therapeutic strategies designed to harness the immune system's cytotoxic potential against malignancies. It encompasses the activation of Natural Killer (NK) cells through specific ligands (e.g., MICA, MICB, ULBPs) that interact with receptors like NKG2D to trigger innate immune responses (Source: UniProt, P19440). Additionally, it includes the engagement of the CD16 (FcγRIII) receptor via the Fc portion of monoclonal antibodies, which is the primary driver of antibody-dependent cellular cytotoxicity (ADCC) (Source: StatPearls, NBK557618). The profile also incorporates tumor-associated antigens (TAAs) targeted by Chimeric Antigen Receptor (CAR) therapies, which allow for the precise redirection of T or NK cells to eliminate tumor cells expressing specific markers like CD19 or BCMA (Source: NIH, NCI Dictionaries). These mechanisms are utilized by a wide range of approved and experimental therapies, including monoclonal antibodies, bispecific killer engagers (BiKEs), and CAR-T/NK cell products, to overcome tumor-induced immunosuppression and achieve durable clinical responses.

Other names

NK cell engager targetsADCC and CAR-T antigensTumor-associated antigens (TAA)NK cell activating ligands

The mechanism involves the tripartite stimulation of immune effector cells: first, by providing ligands that bind to activating NK cell receptors (e.g., NKG2D); second, by utilizing the Fc region of antibodies to cross-link CD16 on NK cells for ADCC; and third, by engineering CARs to recognize specific tumor antigens, thereby bypassing MHC restriction to induce direct cell lysis (Vivier et al., Nature, 2018; June et al., Science, 2018).