A group from The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA, etc. has reported a novel approach using glycoprotein targeted chimeric antigen receptor (CAR)-NK Cells for the treatment of SARS-CoV-2 infection.
NK cells are innate lymphocytes of the immune system with an important role in the control of viral infections, and CAR-T and CAR-NK cells are emerging immunotherapies against cancer and infectious disease with great promise.
Typically, the expressed synthetic receptors on NK cells are designed to bind target surface protein. In this study, authors designed a CAR making use of a unique extracellular moiety (i.e., lectin) with binding properties dependent on target glycosylation. Targeting of glycoprotein, and specifically N-glycosylation products, with a CAR is rare. This is the first CAR targeting the N-glycans dispersed on SARS-CoV-2 Spike protein, and also, this would be the first lectin-based CAR designed and functionally tested in pre-clinical study.
As lectins have evolved over millions of years to be highly potent and selective to glycans, the H84T-BanLec CAR represents an entirely new approach in that it targets aberrant glycosylation patterns (high mannose, in this case) in SARS-CoV-2 viral proteins. Here, Banlec is a lectin which is known to have binding specificity to high mannose which exists in proximity to the receptor binding domain of the envelope SARS-CoV-2 Spike protein.
There is a strong need for the development of CARs with receptor targeting patterns that are less likely to be impacted by genomic point mutations observed in RNA virus such as SARS-CoV-2.