Tumor specific antigen targeted antibody fused with MICA stimulates NKG2D mediated immunosurveillance and exhibits potent anti-tumor activity against malignancies

M class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To trigger NKG2D-mediated immunosurveillance, we designed antibody fusion protein which consisted of human MICA and antibody component. These bispecific proteins maintained the properties of the parental antibodies. Upon binding to the tumor-associated antigens, the MICA portion was expected to promote the recognition of tumor cells by NK cells and to enhance NK cell-mediated cytotoxicity. In tumor-bearing nude mice, these fusion proteins specifically targeted to relevant tumor tissues, where they effectively recruited NK cells and induced the release of cytokines. The MICA based antibody fusion proteins have attractive potentials for clinical applications and this design provides a new approach for tumor-targeting immunotherapy.