Glycoprotein Targeted CAR-NK Cells for the Treatment of SARS-CoV-2 Infection

• DOI: 10.3389/fimmu.2021.763460
• Publication Date: 2021-12-23T07:38:28Z
• Authors: Ilias Christodoulou; Ruyan Rahnama; Jonas W. Ravich; Jaesung Seo; Sergey N. Zolov; Andrew N. Marple; David M. Markovitz; Challice L. Bonifant
• Keywords: 0301 basic medicine; Immunology; Cell- and Tissue-Based Therapy; CAR-NK cells; Cell Line; 03 medical and health sciences; glycobiology; Viral Envelope Proteins; Humans; Banana Lectin; Receptors, Chimeric Antigen; SARS-CoV-2; COVID-19; Musa; RC581-607; 3. Good health; Killer Cells, Natural; HEK293 Cells; Viral Envelope; Spike Glycoprotein, Coronavirus; immunotherapy; Immunotherapy; Immunologic diseases. Allergy; Plant Lectins; Mannose

H84T-Banana Lectin (BanLec) CAR-NK cells bind high mannose glycosites that decorate the SARS-CoV-2 envelope, thereby decreasing cellular infection in a model of SARS-CoV-2. H84T-BanLec are innate effector cells, activated by virus. This novel agent is promising therapeutic, capable clearing circulating virus and infected cells. Banana binds glycans on viral envelopes, exerting an anti-viral effect. A point mutation (H84T) divorces BanLec mitogenicity from antiviral activity. contains proximity to receptor binding domain envelope Spike (S) protein. We designed chimeric antigen (CAR) incorporates as extracellular moiety. Our CAR was devised specifically direct NK cell promote clearance. The stably expressed at density primary human during two weeks ex vivo expansion. reduced S-protein pseudotyped lentiviral 293T expressing ACE2, for were secrete inflammatory cytokines when culture with virally therapy further testing against wild-type models infection. They may represent viable off-the-shelf immunotherapy patients suffering COVID-19.