B6-hCD3/hCD20 Mouse
Product Name
B6-hCD3/hCD20 Mouse
Product ID
C001571
Strain Name
C57BL/6NCya-Cd3tm2(hCD3)Ms4a1em1(hMS4A1)/Cya
Backgroud
C57BL/6NCya
When using this mouse strain in a publication, please cite “B6-hCD3/hCD20 Mouse (Catalog C001571) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
B1, S7, Bp35, CD20, FMC7, CVID5, LEU-16
NCBI ID
Chromosome
Chr 11
MGI ID
Datasheet
Strain Description
Cluster of Differentiation 3 (CD3) is a protein complex that acts as a co-receptor for T cells and is involved in the activation of cytotoxic T cells (CTLs) and helper T cells (THs). CD3 consists of five polypeptide chains: γ, δ, ε, ζ, and η, all of which are transmembrane proteins. The transmembrane regions of CD3 molecules connect with the transmembrane regions of TCR's two polypeptide chains through salt bridges, forming the TCR-CD3 complex, which is essential for T cell antigen recognition [1-2]. After TCR recognizes an antigen, the activation signal is transduced by CD3 into the T cell. CD3 is highly specific at all developmental stages of T cells, thus it is considered a T cell-specific immunohistochemical marker. Additionally, CD3 is present in almost all T cell lymphomas and leukemias and can be used to distinguish between morphologically similar B cell and bone marrow tumors. Due to its significant role in T cell activation and antigen recognition, CD3 is an important drug target in immunosuppressive therapy for type 1 diabetes and other autoimmune diseases [3].
Cluster of Differentiation 20 (CD20), also known as MS4A1, is a functional receptor molecule on the surface of B lymphocytes, closely associated with B cell activation, signal transduction, and growth regulation. CD20 is expressed in the late stages of B cell lymphopoiesis and disappears after differentiation into plasma cells. Therefore, CD20 is expressed from pre-B cells to mature B cells, but not in plasma cells [4]. It is highly expressed in most B-cell lymphomas. Since 1997, the advent of anti-CD20 monoclonal antibodies such as Rituximab has significantly improved the treatment outcomes for B cell malignancies. Therapeutic monoclonal antibodies (mAbs) targeting the CD20 antigen are widely used in research on B cell-depleting tumor therapies to treat various cancers and autoimmune diseases [5-7]. With the development of combination therapies, CD3/CD20 bispecific antibodies have gained significant attention from researchers. These antibodies can bind to CD20 on cancer cells and CD3 on T cells, promoting local T cell activation and cancer cell killing [8]. Currently, four CD3/CD20 bispecific antibodies have been approved for marketing: Epcoritamab (AbbVie/Genmab), Mosunetuzumab (Roche/Biogen), Glofitamab (Roche), and Odronextamab (Regeneron).
The B6-hCD3/hCD20 mouse is obtained by crossbreeding B6-hCD3 mice (Catalog No.: C001325) with B6-hCD20 mice. It can be used for the development of CD3/CD20-targeted drugs, as well as for research in tumor immunotherapy and autoimmune disease-related drugs.
Reference
Dong D, Zheng L, Lin J, Zhang B, Zhu Y, Li N, Xie S, Wang Y, Gao N, Huang Z. Structural basis of assembly of the human T cell receptor-CD3 complex. Nature. 2019 Sep;573(7775):546-552.
Dykhuizen M, Ceman J, Mitchen J, Zayas M, MacDougall A, Helgeland J, Rakasz E, Pauza CD. Importance of the CD3 marker for evaluating changes in rhesus macaque CD4/CD8 T-cell ratios. Cytometry. 2000 May 1;40(1):69-75.
Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, Clark M, Waldmann H. The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol. 1993 Feb;23(2):403-11.
Tedder TF, Engel P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today. 1994 Sep;15(9):450-4.
Pavlasova G, Mraz M. The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy. Haematologica. 2020 Jun;105(6):1494-1506.
van Meerten T, Hagenbeek A. CD20-targeted therapy: the next generation of antibodies. Semin Hematol. 2010 Apr;47(2):199-210.
Boross P, Leusen JH. Mechanisms of action of CD20 antibodies. Am J Cancer Res. 2012;2(6):676-90. Epub 2012 Nov 20.
Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, Yan X, Clark R, Reyes A, Stefanich E, Mai E, Young J, Johnson C, Huseni M, Wang X, Chen Y, Wang P, Wang H, Dybdal N, Chu YW, Chiorazzi N, Scheer JM, Junttila T, Totpal K, Dennis MS, Ebens AJ. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015 May 13;7(287):287ra70.
Strain Strategy
Figure 1. Diagram of the gene editing strategy for the generation of B6-hCD3 mice. The mouse Cd3e, Cd3d, and Cd3g genes which encode the three components of the CD3 complex, Cd3ε, Cd3δ, and Cd3γ, were replaced by the corresponding human homologous genes.
Figure 2. Diagram of the gene editing strategy for the generation of B6-hCD20 mice. The sequences from the ATG start codon to TAA stop codon of the endogenous mouse Ms4a1 gene were replaced with the sequences from the ATG start codon to TAA stop codon of the human MS4A1 gene.
Application Area
Development and Evaluation of CD3/CD20-Targeted Drugs;
Tumor Immunotherapy Research;
Immunosuppressive Therapy Research for Autoimmune Diseases.
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