CD200/CD200R Screening Model
00与CD20
CD200 and CD200R
CD200 (also known as OX-2) is a member of the Ig superfamily (IgSF), which is similar in structure to B7 family proteins, and it contains two extracellular immunoglobulin domains and a small 19-amino acid Intracellular domain, no known signaling motifs. CD200 is expressed in a variety of normal tissues, including immune cells such as B lymphocytes and activated T lymphocytes. Studies in recent years have shown that CD200 is also overexpressed in a variety of human cancer cells, including human melanoma, ovarian cancer, glioma, myeloid leukemia, some B cell malignancies and most endocrine malignancies ( such as small cell lung cancer). As the homologous ligand of CD200, CD200R is also an IgSF protein. In mice and humans, the expression pattern of CD200R is similar, and it is highly expressed in macrophages, neutrophils and mast cells. Unlike most IgSF receptors, CD200R lacks an ITIM domain; however, its 67 amino acid cytoplasmic tail contains three tyrosine residues, the third of which is located within the NPXY motif, which After CD200R binds to the ligand, it will be phosphorylated, which leads to it not directly recruiting SHP1, SHP2 and other protein tyrosine phosphatases or phosphorylated inositol phosphatase (SHIP), but recruiting tyrosine kinases for downstream engagement Proteins Dok-2 and 1, which then bind to RasGAP and SHIP. In macrophages and mast cells, this cascade has been shown to inhibit the phosphorylation of ERK, p38, and JNK, and to suppress the activation of myeloid cells. Although CD200R expression is mainly found in macrophages and neutrophils, further studies have shown that CD200R expression is also present in dendritic cells (DC) and some T cell subsets, suggesting that CD200R signaling in these cell types may also have an adjustment function.
CD200 is found to be overexpressed in a variety of solid and hematological tumor cell types and is also expressed at high levels on cancer stem cells. The combination of CD200 and its receptor CD200R will generate multiple immunosuppressive signals, effectively inhibit T cell immune response and natural killer (NK) cytotoxic activity, and promote macrophages to secrete indoleamine-2, 3 dioxygenase IDO (a Immunosuppression of tryptophan catabolic enzymes) and triggers regulatory T cell (Treg) expansion, suggesting that CD200 and its receptor CD200R are a potential inhibitory immune checkpoint target by blocking the binding of CD200 to CD200R The mechanism of action and signal transmission may be used in the development of new anti-tumor immune checkpoint drugs. Existing studies have also shown that CD200-blocking antibodies can increase the levels of interleukin-2 (IL-2) and interferon-γ (IFN-γ) after adding primary CLL cells to mixed lymphocyte reactions in vitro , restored Th1 response and inhibited Treg; and in animal models, it was further proved that CD200-blocking antibody treatment could restore lymphocyte-mediated anti-tumor response in vivo.
Samalizumab is a new type of recombinant humanized monoclonal antibody (mAb), which can specifically bind to CD200 and block its binding to the CD200 receptor (CD200R). CD200 signaling anticancer drug, in a phase I study, 23 patients with advanced chronic lymphocytic leukemia (CLL) and 3 patients with multiple myeloma (MM) received injections of the drug, although only in some CLL patients However, this study still provides some clinical rationale for targeted inhibition of the immune checkpoint CD200/CD20OR.
Cellular Screening Model for CD200/CD200R Targets
For the development of this potential immune checkpoint target drug, Kebai Biotech has specially developed a cell screening model for CD200/CD200R target, which can measure the activity and evaluate the efficacy of CD200/CD200R antibody at the cellular level. Products The information and related data are as follows:
CD200R Effector Reporter cell RQP74179
CD200 Target cell RQP74180
Figure 1. Dose Response of CD200R Blocking Ab in CD200R Effector Reporter Cells (C34) With CD200 Target cells (C18).
