MHC class I-related chain A (MICA)

MHC class I-related chain A (MICA) is a stress-induced cell surface glycoprotein that belongs to the non-classical MHC class I family [6, 8]. Unlike traditional MHC molecules, it does not present peptides or associate with beta-2 microglobulin, instead acting as a primary ligand for the activating receptor NKG2D (KLRK1) found on natural killer (NK) cells and T cells [8, 13]. MICA is typically absent from healthy tissues but becomes significantly upregulated under conditions of cellular stress, such as DNA damage, oxidative stress, or malignant transformation [6, 15]. In cancer, tumor cells often evade immune detection by enzymatically shedding MICA from their surface using metalloproteinases like ADAM10 and ADAM17, which results in soluble MICA (sMICA) that functions as an immunosuppressive decoy [1, 6]. Therapeutic strategies targeting MICA focus on monoclonal antibodies, such as CLN-619, which bind to the MICA alpha-3 domain to inhibit this shedding and stabilize surface expression [2, 5]. By maintaining MICA on the tumor surface, these therapies restore the NKG2D-mediated "kill-me" signal and can further promote tumor cell lysis via antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) [1, 4]. Serum levels of soluble MICA are utilized as critical biomarkers for monitoring disease progression and the efficacy of MICA-targeted interventions [11, 17].

Other names

MIC-APERB11.1MHC class I polypeptide-related sequence A

Prevention of proteolytic shedding by binding to the alpha-3 domain, stabilization of surface MICA expression to restore the NKG2D-mediated immune activation axis, and induction of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).