Cancer immunotherapy, utilizing the abilities of the immune system to treat cancer, is rapidly becoming the standard of care for many malignancies and offers the best hope for curing cancer patients. The immune system contains lots of inhibitory pathways (immune checkpoints) that are necessary to prevent an uncontrolled immune response as well as to control its severity and length. While cancer cells typically express a number of neo-antigens that would normally be recognized by the immune system as foreign and warrant the cells elimination, cancer cells also express ligands that bind to and exploit these immune checkpoints to induce tolerance. The blockade of immune checkpoint has proved to be a promising approach that leads to extraordinary increases in overall survival. Creative Biolabs, a leading provider in the field of antibody discovery, is proud to provide specialty humanized immune checkpoint knock-in mice to facilitate diverse immunotherapy development for our worldwide clients, including CD4.
CD4 Immune Checkpoint Receptor
CD4 (cluster of differentiation 4), a member of the immunoglobulin supergene family, is an integral membrane glycoprotein expressed on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. Over 50% of the peripheral blood T-cells and bone marrow cells are CD4+, representing the helper/inducer subtype. Most of post-thymic T-cell neoplasms are CD4-positive. CD4+ T helper cells (often referred to as CD4 cells, T-helper cells or T4 cell) are white blood cells and have been identified as an essential part of the human immune system. CD4 serves multiple functions in responses against both external and internal offenses.
The Mechanism and Significance of CD4 Signaling Pathway
CD4 functions primarily as a co-receptor in MHC class II-restricted T-cell activation. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. CD4 expressed on T cells interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs) and sequentially recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates eventually leading to lymphokine production, motility, adhesion and activation of T-helper cells. When expressed on other cells such as macrophages or NK cells, CD4 plays a vital role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway, and it also participates in the development of T-helper cells in the thymus and activates the differentiation of monocytes into functional mature macrophages.
Development of Humanized CD4 Immune Checkpoint Knock-In Mice
CD4 is the primary receptor for HIV retroviruses and plays a crucial functional role in the course of human immunodeficiency virus 1 (HIV-1) infection. Recent studies have shown that the CD4 protein is not only the cellular receptor for HIV-1 but also participates actively in post-binding events significant for infection and cell fusion. In Creative Biolabs, scientists go all out to develop a wide range of well-characterized Magic™ “humanized” animal models, which can provide you with humanized immune checkpoint knock-in mouse models including humanized CD4 knock-in mouse. Please feel free to contact us for more detailed information.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
For Research Use Only.
