MHC class I polypeptide-related sequence B (MICB) (MICB)

MHC class I polypeptide-related sequence B (MICB) is a stress-induced protein that acts as a ligand for the activating receptor NKG2D found on natural killer (NK) cells and various T cell subsets [1, 2]. While MICB is minimally expressed on healthy tissues, it is significantly upregulated on the surface of cells undergoing malignant transformation or viral infection, serving as a signal for immune-mediated elimination [5, 9]. However, many tumors evade this surveillance by employing metalloproteases such as ADAM10 and ADAM17 to shed MICB from their surface, creating soluble MICB (sMICB) that can downregulate NKG2D and desensitize effector cells [1, 24]. In therapeutic development, monoclonal antibodies such as CLN-619 and AHA-1031 target the alpha-3 domain of MICB to prevent this shedding, thereby stabilizing its surface expression and re-engaging the host immune response against cancer cells [3, 11]. These treatments often utilize dual mechanisms, including the restoration of NKG2D-mediated surveillance and the induction of antibody-dependent cellular cytotoxicity (ADCC) [3, 9]. Current clinical investigations focus on using MICB-targeted agents for advanced solid tumors and hematologic malignancies, often in combination with other immune checkpoint inhibitors to overcome tumor evasion mechanisms [11, 14].

Other names

MHC class I-related chain BMIC-BPERB11.2

Inhibition of proteolytic shedding from the cell surface, stabilization of membrane-bound expression to enhance NKG2D receptor engagement, and induction of antibody-dependent cellular cytotoxicity (ADCC).