On November 30, 2021 Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, reported the publication of preclinical data regarding application of its proprietary Block–Removed Immunoglobulin Technology (BRITE) to enhance the efficacy of the CD20-targeting rituximab antibody in the presence of the immunosuppressive CA125 protein (Press release, Navrogen, NOV 30, 2021, View Source [SID1234596296]). The peer-reviewed study was published in Oncology Letters (www.spandidos-publications.com/10.3892/ol.2021.13120).
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The study results showed that CA125 can directly bind rituximab and suppress its immune-effector complement–dependent cytotoxicity (CDC) and antibody–dependent cellular cytotoxicity (ADCC) mechanisms of action. Recent clinical evidence suggests that high serum levels of CA125 reduce the effectiveness of rituximab’s clinical activity in patients with follicular lymphoma. In an attempt to overcome CA125-mediated suppression, BRITE was applied to generate antibody variants that were refractory to CA125 binding and retained efficient CDC and ADCC activity in the presence of CA125. BRITE is an engineering platform that generates and selects for proteins that are refractory to immunosuppressive factors. The application of BRITE resulted in the discovery of an antibody (NAV-006) with a single amino acid change that was refractory to CA125 immunosuppression while retaining similar antigen binding and immune-effector activities as the parental rituximab.
Dr. Luigi Grasso, Chief Scientific Officer of Navrogen said, "the findings here are another demonstration of the humoral immunosuppressive effects that proteins such as CA125 can have on antibody-mediated therapies and the opportunities that BRITE technology can bring to overcome their impact. Our BRITE-optimized rituximab NAV-006 will offer a new opportunity to treat CA125-positive follicular lymphoma patients in our efforts to combat this disease."
Navrogen is actively applying BRITE to improve other therapeutic antibodies affected by immunosuppressive factors for internal pipeline candidates and 3rd party collaborators.