Global assessment of CD24Fc activity on human immune system

CD24Fc is a recombinant fusion protein consisting of the extracellular domain of mature human CD24 linked to the human immunoglobulin G1 (IgG1) Fc domain. Preclinical studies have demonstrated that CD24Fc provide therapeutic effect for autoimmune diseases and graft-vs-host diseases. These studies prompted clinical development of CD24Fc for immunological diseases. As the first-in-human (FIH) study, CD24Fc was tested in a phase I, randomized, double-blind, placebo-controlled, single ascending dose study for safety and pharmacokinetics in healthy people. For global assessment of CD24Fc activity on host immune system, we collected the peripheral blood mononuclear cells (PBMC) from human subjects in CD24Fc phase I clinical study and performed RNA-sequencing for PBMC samples. We found that CD24Fc treatment significantly reduced the transcripts of genes encoding pattern recognition receptors, inflammatory cytokines, chemokines and their receptors. To investigate the role of CD24Fc on host immune system, we collected the PBMC from human subjects in CD24Fc phase I clinical study, then performed RNA-sequencing for PBMC samples obtained on Day -1 (pre-treatment) and Day 3 (post-treatment) from subjects receiving 240 mg of CD24Fc. Of the samples collected from 6 patients, 4 pairs of RNA samples passed quality control and were subject to RNAseq.