Recently, Cullinan Oncology announced that the FDA has approved Cullinan Oncology's CLN-619 New Drug Clinical Research Application (IND). CLN-619 is a monoclonal antibody that activates natural killer cells (NK) and T cells through the MICA/B-NKG2D axis, and then exerts anti-tumor activity. It has therapeutic potential for solid tumors and hematological tumors. CLN-619 will also be the first MICA antibody drug to enter human clinical trials.

CLN-619 is a humanized IgG1 monoclonal antibody that can bind to MICA/B expressed on a variety of cancer cells. MICA/B is the innate immunity and adaptation of NK cells, CD8+ T cells, and γ/δ T cells. The NKG2D receptor on the surface of sexual immune cells induces a ligand for stress. In order to avoid being lysed by these immune cells, tumor cells will actively shed MICA/B protein on their surface. CLN-619 enhances anti-tumor activity through multiple mechanisms of action, including preventing the proteolytic release of MICA/B from tumor cells, antibody-dependent cell-mediated cytotoxicity (ADCC), enhancing the binding and mitigation of MICA/B and NKG2D Inhibition of MICA/B shedding.

In preclinical studies, animal model data of CLN-619 monotherapy showed significant tumor growth inhibitory effects and a reduction in serum soluble MICA levels.