Tumor-derived soluble MICA (sMICA) and its allelic diversity impair immune responses by disrupting NKG2D function and promoting immune evasion, highlighting the need for antibody-based strategies targeting the MICA/NKG2D axis.<h4>Methods</h4>We generated a fully human IgG1 monoclonal antibody targeting the α1 domain of MICA using phage display and rational epitope design focused on a conserved, low-polymorphic region. The gene discussed is KLRK1; the disease is neoplasm.