After years of exploration and efforts, tumor immunotherapy has entered a brand-new stage, bringing revolutionary changes to antibody drug development. Following the recognition of a new class of tumor targets – immune checkpoints, humanized immune checkpoint knock-in mice have emerged as critical tools for various preclinical evaluation. Based on our unparalleled transgenic mice platform, Creative Biolabs has developed a wide range of humanized mouse models (e.g. PD-1, PD-L1, CD28, and CD47) to facilitate the discovery and development of leading-edge immune checkpoint modulator drugs. Currently, our scientists are pleased to present our exclusive Magic™ humanized BTLA immune checkpoint knock-in mice to our worldwide clients.

BTLA immune checkpoint pathway

B- and T- lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed by T cells. BTLA can be induced by activation of naïve T cells and is expressed by developing TH1 and TH2 cells. When highly polarized, TH2 cells will lose BTLA expression while TH1 cells still keep expressing BTLA. Herpes virus entry mediator (HVEM) is a ligand for BTLA. It is expressed on T cells, B cells, NK cells, DCs, myeloid cells. BTLA ligation by HVEM negatively regulates T-cell immune responses.

BTLA has three cytoplasmic tyrosine-containing motifs with one predicted for GRB2 recruitment and the other two both have immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences. Tyrosine residues in ITIM motifs can be phosphorylated and both ITIMs are requisite to recruit the tyrosine phosphatases SHP1 and SHP2. It's still unclear at present which kind of targets SHP1 and SHP2 recruited to BTLA, but it is supposed to downregulate proximal TCR signaling.

So far, it is reported that BTLA immune checkpoint pathway reduces T-cell activation according to following facts:

  • If crosslinked by specific antibodies, BTLA on T cells can inhibit T-cell proliferation;
  • Using CHO cells expressing HVEM, antigen-specific priming analysis proved that BTLA immune checkpoint pathway reduced T-cell proliferation;
  • T-cell proliferation can be inhibited via activation of CD28 by CD80 expressed by CHO cells through BTLA pathway at high antigen doses, but have no influence on the inhibition of T-cell proliferation at low antigen doses;
  • In other studies, an agonistic BTLA-specific antibody was found to inhibit CD25 expression on the T-cells, partly due to a blockade in IL-2 secretion, but do not affect another activation marker, CD69, or cause apoptosis.

Development of Human BTLA Immune Checkpoint Knock-In Mice

Magic™ Humanized BTLA Immune Checkpoint Knock-In Mice

As is known, inhibition of the BTLA-HVEM pathway is now being explored as an efficient way to argue the response of immune system against tumor. Using the KI mouse models to figure out the function of BTLA is a critical measure for researchers to discovery checkpoint blockers targeting human checkpoints and evaluate the drug efficacy. In comparison to the ordinary mouse, our unique Magic™ mouse model has many advantageous features: it carries a 100% human BTLA gene which eliminates the human-to-mouse deviation in regard to drug targets; meanwhile, unlike other humanized mice, it maintains an intact immune system that helps to better predict drug efficacy and side effects. With rich experience in the transgenic animal modeling field, we now guarantee the high knock-in efficiency with no other genes compromised.

Except for BTLA, Creative Biolabs has launched a broad series of humanized immune checkpoint mice to satisfy diverse research demands. We also offer multiple other Humanized Mouse Models you may be interested in:

• Humanized PBL SCID Mice
• Humanized SRC SCID Mice
• Humanized BLT Mice
• Humanized Immune Checkpoint knock-in Mouse Models

Meanwhile, we can also provide a broad range of immune checkpoint mouse models, including but not limited to:

Please feel free to contact us for more details.

For Research Use Only.


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