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Aya Jakobovits
Abgenix, Inc.
Fremont, CA

XenoMouse™ - A Robust Technology for Production of Therapeutic Human Monoclonal Antibodies

XenoMouse™ is a mouse strain engineered to produce human antibodies in the place of mouse antibodies by introduction of megabase-sized fragments of the human heavy and kappa light chain loci into the germline of mice deficient in mouse antibody production. Together, these fragments contained the majority of the human antibody gene repertoire including 66 VH and 32 Vk genes. This strategy was used to generate three XenoMouse strains (G2, G4 and G1) containing different human g constant regions and secreting human IgG2k, IgG4k or IgG1k antibodies, respectively. The human humoral response in these mice closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enable XenoMouse™ to generate high affinity fully human antibodies to multiple antigens, including human antigens such as IL-8, EGF receptor, TNFa, L-selectin, and Groa. XenoMouse™-derived hybridomas were shown to be stable and to produce significant levels of human monoclonal antibodies. Characterization of these hybridomas and their derived therapeutic human monoclonal antibodies will be presented.

References:

1. Mendez, M. J. et al. (1997) Nature Genet 15, 146-156.

2. Tsuda et al. (1997) Genomics 42, 413-421.

3. Mendez, M. J. et al. (1995) Genomics 26, 294-307.

4. Green, L. L. et al. (1994) Nature Genet 17, 13-21.

5. Jakobovits, A. et al. (1993) Nature 362, 255-258.

6. Jakobovits, A. et al. (1993) Proc Natl Acad Sci USA 90, 2551-2555.