Perspective abstract


Nature Biotechnology 25, 1134 - 1143 (2007)
Published online: 5 October 2007 | doi:10.1038/nbt1337

From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice

Aya Jakobovits1, Rafael G Amado2, Xiaodong Yang3, Lorin Roskos4 & Gisela Schwab5


Therapeutic monoclonal antibodies have shown limited efficacy and safety owing to immunogenicity of mouse sequences in humans. Among the approaches developed to overcome these hurdles were transgenic mice genetically engineered with a 'humanized' humoral immune system. One such transgenic system, the XenoMouse, has succeeded in recapitulating the human antibody response in mice, by introducing nearly the entire human immunoglobulin loci into the germ line of mice with inactivated mouse antibody machinery. XenoMouse strains have been used to generate numerous high-affinity, fully human antibodies to targets in multiple disease indications, many of which are progressing in clinical development. However, validation of the technology has awaited the recent regulatory approval of panitumumab (Vectibix), a fully human antibody directed against epidermal growth factor receptor (EGFR), as treatment for people with advanced colorectal cancer. The successful development of panitumumab represents a milestone for mice engineered with a human humoral immune system and their future applications.

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  1. Agensys, Inc., 2225 Colorado Blvd., Santa Monica, California 90404, USA.
  2. Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA.
  3. Intradigm Corporation, 3350 West Bayshore Road, Palo Alto, California 94303, USA.
  4. AstraZeneca Pharmaceuticals LP, 24500 Clawiter Road, Hayward, California 94545, USA.
  5. Exelixis, Inc., 170 Harbor Way, S. San Francisco, California 94083, USA.

Correspondence to: Aya Jakobovits1 e-mail: ajakobovits@agensys.com



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