MicAbody™ proteins

immuno-Oncology-slidesMICA is a molecule only expressed by stressed cells (e.g., cancer, virus-infected, etc.) that signals to the immune system to eliminate that cell. In contrast, the NKG2D molecule (‘immunoreceptor’) has a common activating role among the innate and adaptive immune systems, both of which are critical for effective tumor eradication and viral clearance. Immune cells use the NKG2D receptor to recognize malignant or virus-infected cells that display the MICA stress molecule. Upon binding MICA, NKG2D triggers prompt killing of the dangerous, stressed cell. In many advanced cancers and chronic viral infections disease-mediated mechanisms reduce or eliminate cell surface MICA in order to evade immune detection.

Figure A

To overcome this immune evasion we have developed MicAbody™ proteins; engineered MICA α1-α2 effector domains that very tightly bind the NKG2D receptor with unprecedented potency, which are then fused to tumor specific antibodies. MicAbody proteins bind NKG2D with high affinity and can simultaneously bind to a chosen disease specific cell surface antigen. This dual binding activity instructs immune cells to destroy the targeted cancerous or virus-infected cells.

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Our research has shown that our MicAbody proteins can be formatted to target virtually any cell surface antigen and optimized with the proper α1-α2 effector domain to potently redirect the immune system to kill cancer and virus-infected cells. We believe there is tremendous opportunity for Micabody proteins as first-in-class agents that can also combine with checkpoint blockade, antibody ADCC, ADCs, and CD3 bispecific therapeutics.