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 virus-infected cells fail to express sufficient levels of the stress signal, MICA, and thereby escape natural immune surveillance. MicAbody proteins are designed to overcome this escape mechanism.

immuno-Oncology-slidesInnate and adaptive immune cells, specifically Natural Killer cells and certain T cells, use the NKG2D receptor to detect and eliminate virally infected cells that are decorated with MICA on their surface. The rationale for therapeutically engaging the NKG2D-MICA pathway to fight viral diseases is supported by more than a decade of research demonstrating the importance of this interaction to prevent virus spread and facilitate clearance of viruses.

NKG2D-dependent killing of infected cells is highly efficient, and as one would anticipate, viruses have evolved elaborate mechanisms to reduce or eliminate MICA expression in order to escape the wrath of the immune system. We are to overcoming this escape by developing antibody-based, targeted immunotherapeutic agents (MicAbody proteins) that can simultaneously engage NKG2D as well as specific viral antigens on cells, such as on those lacking adequate levels of surface MICA. This approach redirects and activates the killing potency of NKG2D-expressing immune cells specifically towards the escaped virus-infected cells.