PLX077419

GSE109542: Antibody-Mediated Inhibition of MICA/B Shedding Promotes NK Cell-Driven Tumor Immunity

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

MICA and MICB (MICA/B) are expressed by many human cancers due to cellular stress and tag cells for elimination by cytotoxic lymphocytes through NKG2D receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA/B proteins. We rationally designed antibodies targeting the MICA 3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA/B by human cancer cells. These antibodies inhibited tumor growth in multiple fully immuno-competent mouse models and also reduced human melanoma metastases in a humanized mouse model. Anti-tumor immunity was mediated mainly by NK cells through activation of NKG2D and CD16 Fc receptors. This novel approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity. SOURCE: Lucas Ferrari de Andrade (lucas_ferrarideandrade@dfci.harvard.edu) - Dana-Farber Cancer Institute