Identification of a Robust Antibody Modulator of CD33 in In Vitro Models

Abstract

CD33 is a sialic acid binding immunoglobulin-type lectin found on myeloid cells throughout the body, including microglia, the brain’s resident immune cells. CD33 has been implicated genetically in late-onset Alzheimer’s disease (LOAD) as both a potential risk factor and potential protective factor. This is based on the alternative splicing of CD33, which produces two isoforms of the protein: a full-length isoform, and a shorter isoform lacking the extracellular sialic acid binding domain. Because of its implication in disease, CD33 may be a potential therapeutic target for AD. A previous study by Wißfeld, et al. (2021) has designed a reporter cell assay capable of monitoring CD33 activation. Using this model, we were able to identify a robust antibody modulator of CD33, rabbit monoclonal E6V7H. Endogenous models expressing CD33, THP-1 and TF- 1, were also tested using E6V7H for CD33 activation. We found that treating these cells with E6V7H altered the expression levels of downstream phospho-SHP-1, but more work needs to be done on the downstream signaling of CD33 to create an endogenous readout of CD33 activation.