Magic™ Humanized Immune Checkpoint Mice

As a leading innovator as well as a long-term dedicated service provider, Creative Biolabs has successfully launched, commercialized and optimized an exclusive Magic™ therapeutic antibody discovery platform using a variety of state-of-the-art technologies. Particularly, we now provide specialty human immune checkpoint knock-in mice to facilitate diverse immunotherapy development for our worldwide clients.

Tumor cells have multiple mechanisms to escape from host immune surveillance and elimination. One major evading mechanism is to interfere with costimulatory/inhibitory signal balance in the process of TCR activation, which can effectively induce immune suppression. This is achieved by a group of membrane proteins expressing on immune effector cells (e.g. T/B cell, NK cell). Extensive research and preclinical/clinical data highlight the promising therapeutic potential of monoclonal antibodies against those “checkpoints” to re-motivate the immune system to destroy tumors. Recently, they have gained increasing research interest, and many immune checkpoint blockers are approved by FDA or in late clinical trials.

With the rapid pace of anti-tumor drug development, there evolve urgent requirements for sophisticated animal models to more accurately recapitulate in vivo pharmacodynamics/pharmacokinetic/toxicity profile. Currently, many oncology studies have been explored in human tumor xenografts growing in immunodeficient mice. However, for immunomodulatory agents like immune checkpoint blockers, this approach can be inadequate due to the lack of human immune system as well as tumor microenvironment. While it can be extremely expensive and time-consuming to develop a fully human immune system via engraftment of human HSC/PBMC, we offer a novel alternative of human knock-in (KI) immune checkpoint genes to test drugs that target human immune cells.

With extensive experience in constructing transgenic animals, Creative Biolabs has integrated a serial of well-established human immune checkpoint KI mouse models.

Fig.1 Features of Magic™ Humanized Immune Checkpoint KI Mouse Model.

Features of Magic™ Humanized Immune Checkpoint KI Mouse Model

• C57BL/6 genetic background: the most widely utilized inbred mouse strain in diverse biology, immunology, and oncology research. High accuracy, good comparability, and homogeneous reactions are generally observed.
• Precise humanized gene loci: all factors that potentially interfere with humanized gene expression will be taken into consideration, evaluated and designed with precise control. Native and specific confirmation of the target protein, especially the binding region, can be guaranteed.
• Highly efficient models: Comprehensive QC and validations with clinical grade checkpoint blockers have been performed to make sure adequate expression and proper signal transduction of human immune checkpoint genes.
• Fully functional and potent immune system: the intact murine immune system will not be compromised, while the immune cells will express human version of checkpoints of interest.
• Immune effector function investigation: this model also provides the opportunity to explore the capacity of checkpoint antibodies to elicit cell-mediated cytotoxic effector function (such as ADCC and ADCP), if engineered with human Fcγ receptors. As is known, multiple Fcγ receptors can participate in activating/inhibiting immune functions. Checkpoint blockers with different human Fc thus can be tested in human KI mice to select appropriate IgG isotype with strongest anti-tumor effects and least toxicity.
• Autoimmune or pro-inflammatory side-effect evaluation: due to the sound immune system and “humanized” target molecule, it's more predictable of potential side effects like autoimmune/pro-inflammatory potencies of antibody candidates, compared to other mouse models. This is also the most important advantage of our unique Magic™ human KI mouse.

Currently, we offer our unparalleled Magic™ human KI mice with a broad range of immune checkpoints, and the number is still increasing. We are also happy to construct custom transgenic mice/rats upon request.

Creative Biolabs has been making constant commitment to providing best-in-class humanized mice/rats for therapeutic antibody in vivo evaluation to our global customers. Besides, we now provide a variety of other Humanized Mouse Models you may be interested in:

If you are interested in our Magic™ mouse models, please contact us for more details.

For Research Use Only.