MICA is a molecule that, in a normal functioning system, is expressed by stressed cells (e.g., cancer, virus-infected, etc.) signaling to the immune system to eliminate that cell. Many advanced cancers fail to express sufficient levels of the stress signal, MICA, and thereby escape natural immune surveillance. MicAbody proteins are engineered from natural MICA to overcome the escape mechanisms. Innate and adaptive immune cells, specifically Natural Killer cells and certain T-cells, use the NKG2D receptor to detect and eliminate malignant cells decorated on their surface with MICA. The rationale for therapeutically engaging this pathway for immuno-oncology is supported by more than a decade of research demonstrating that this interaction is a critical immune-surveillance pathway that greatly facilitates tumor elimination in vivo.
Because NKG2D-dependent tumor killing is highly efficient, there is strong selective pressure for cancer cells to reduce or eliminate their MICA expression to escape the wrath of the immune system. We are overcoming this escape by developing antibody-based, targeted immunotherapeutic agents (MicAbody proteins) that can simultaneously engage the NKG2D receptor as well as specific tumor cells, thereby redirecting the killing potency of NKG2D-expressing cells to specific tumor cells. Importantly, there is tremendous potential for our MicAbody proteins to synergize with checkpoint blockade drugs and other exciting biopharmaceutical therapies. MicAbody proteins as potential biopharmaceutical agents enable the controlled, very tight arming of the critical NKG2D receptors on cells of innate and adaptive immunity with specific targeting domains and without deploying autologous gene therapy methods.