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Magic™ Human Antibody Production Using Transgenic Mice

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As one forward-looking research institute as well as a leading 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.

Construction of transgenic mouse strains Fig.1 Construction of transgenic mouse strains. (Jakobovits A, Amado RG, et al. 2007)

Since the first EGFR targeting antibody panitumumab (Vectibix) from humanized mice has obtained regulatory approval in 2005, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., CD20 (Ofatumumab), CD4 (Zanolimumab), 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.

Evolution of therapeutic antibody technology and progress to the clinic 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:


Creative Biolabs is now accessible to multiple well-established transgenic mouse/rats 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 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 a most appropriate plan for your project. Please feel free to inquiry us for more details.

References

  1. Jakobovits A, Amado RG, et al. (2007) “From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice.” Nat Biotechnol. 25(10):1134-43.
  2. Lonberg N. (2005) “Human antibodies from transgenic animals.” Nat Biotechnol. 23(9):1117-25.



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