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Fully Human Antibody Discovery: Why Transgenic Mice?

Transgenic Mice Technology Background

In 1975, the discovery of the hybridoma method for isolating monoclonal antibodies (mAbs) from rodents with high specificity and high affinity opened the door for a new class of therapeutic compounds with a wide range of potential disease indications. In 1986, U.S. regulators approved anti-CD3 mAb for the treatment of renal transplant rejection. However, although anti-CD3 mAb is an effective immunosuppressive drug, it is actually an inherent immunogenic molecule. Because rodent antibodies are exotic proteins, the human immune system reacts to them, resulting in rapid clearance, reduced efficacy and increased risk of infusion reactions. Transgenic mouse strains containing a human immunoglobulin library represent an alternative platform technology for the discovery of therapeutic monoclonal antibodies with low immunogenicity. Compared with antibody engineering techniques involving downstream modification and optimization of individual protein molecules, transgenic technology is used for upstream genetic engineering of mouse strains and then used as a drug discovery tool to directly generate human sequence antibodies without further optimization and can be directly introduced into clinical practice. Twelve years after appearing in the scientific literature, immunoglobulin transgenic mice have now been verified as a drug discovery platform with regulatory approval for their first product targeting RGFR.

Overview of the strategies for therapeutic antibody development. (Creative Biolabs Original) Fig. 1 General approaches for the development of therapeutic antibodies

Our therapeutic antibody discovery services:

Advantages and Disadvantages of Transgenic Mice

The main advantage of obtaining complete human antibodies from transgenic mice is that it is superior to other techniques for producing monoclonal antibodies against normal proteins. Because the system of transgenic mice to recognize antigens and produce antibodies remains intact, and it is easy to recognize human proteins as foreign bodies. In addition, because antibodies are produced in vivo, they undergo a normal process of assembly and maturation, thus ensuring that the resulting product has a high target binding affinity.

However, there are some shortcomings in the technology of transgenic mice at present. First of all, immune tolerance is still a problem. Although the immune response can be enhanced through adjuvants and customized immunization methods, it is still difficult to obtain high-affinity antibodies against certain human antigens. The second is the interference of mouse antibodies. Third, it is difficult to immunize with toxic antigens.

The Major Transgenic Mouse Platforms

Our diverse human antibody discovery platforms:

Partially Approved Human mAbs

With the continuous optimization and upgrading of technology, dozens of antibody-based drugs approved by regulators have been produced through the transgenic mice platform. We offer high-quality antibodies in multiple formats against these approved targets, including but not limited to the following:

What Can Creative Biolabs Do?

Empowered by state-of-the-art transgene technology, Creative Biolabs has launched an innovative transgenic mouse strain producing 100% human antibodies (including Fc regions). Apart from this, high immune performance can also be guaranteed. We have successfully generated three humanized transgenic mouse strains capable of producing human antibodies with VH-VL, heavy chains only, and constant VL. Immunization tests reveal this mouse model can react potently to many targets (e.g., cytokines, viral proteins, and membrane proteins). Incorporated with multiple antibody discovery methodologies like hybridoma, phage display, and B cell sorting, humanized mice can be a powerful toolbox to streamline the antibody drug discovery pipeline.


All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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