Transgenic Mice based Magic™ Human Antibody Discovery Services

As one forward-looking custom service provider, Creative Biolabs has established the innovative Magic™ Human Antibody Discovery Platform using transgenic mice/rats. We have integrated multiple first-class "humanized" animals, in combination with our elegant antibody generation technologies, to contribute the discovery and development of fully human antibodies for global clients.

By introducing human immunoglobulin loci (heavy and light chains) into the mouse germlines with inactivated/disrupted endogenous antibody machinery, the transgenic mouse/rat strains can directly generate high affinity, fully human antibodies, which avoid the subsequent costly and tedious in vitro humanization and affinity maturation process. Upon immunization, the Ig transgenes will undergo V(D)J rearrangement, random nucleotide (N region) addition, class switching, and somatic hypermutation to yield impeccable antibodies. This technology takes advantage of the naturally intact immune system with robust response, high-efficient selection and in vivo maturation while maintaining fully humanness which can eliminate immunogenicity concerns.

Fig.1 Construction of transgenic mouse strains.

Since the first EGFR targeting antibody from humanized mice has obtained regulatory approval in 2005, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., anti-CD20, anti-CD4, anti-CD70, etc. These genetically "humanized" animals have become one of the most powerful strategies for therapeutic/diagnostic antibody development, which is now the fastest-growing group of mAb drugs in clinical trials currently.

Fig.2 Evolution of therapeutic antibody technology and progress to the clinic. (Lonberg N. 2005)

Compared with conventional approaches, using transgenic animals can offer following advantages:

More robust antibody production (in vivo immune machinery compared to artificial engineering process)
Optimized properties due to in vivo selection and affinity maturation
No need for tedious and risky humanization and affinity improvement
Low immune tolerance to human antigens (rodent background)
Easy to operate

Creative Biolabs is now accessible to multiple well-established transgenic mouse/rat strains with different genetic backgrounds to allow selecting over different antibody repertoires. In addition, these "humanized" animals have been optimized to enable strong and potent immune responses. Both conventional Igs and human sdAbs can be generated from these transgenic mice. A series of impressive success records against a variety of targets (e.g. cytokines, viral proteins, membrane receptors, etc.) can be tracked.

Equipped with these unparalleled resources, Magic™ human antibody platform provides one-round services utilizing several state-of-the-art technologies for the discovery of impeccable antibody candidates, including transgenic mouse/rat hybridoma technology, transgenic phage display library technology, as well as Native™ antibody discovery platform (plasma cell sorting), to facilitate diverse research objectives.

With vast experience and enthusiasm in human antibody development and engineering, Creative Biolabs has always been devoted to delivering best-in-class services to our worldwide customers. Our scientists are happy to discuss with you to tailor the most appropriate plan for your project. Please feel free to contact us for more details.

Reference

Lonberg N. (2005) "Human antibodies from transgenic animals." Nat Biotechnol. 23(9):1117-25.

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

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