Have we overestimated the benefit of human(ized) antibodies?

Daniel R. Getts, Meghann T. Getts, Derrick P. McCarthy, Emily M.L. Chastain, Stephen D Miller

Research output: Contribution to journalReview article

69 Scopus citations

Abstract

The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.

Original languageEnglish (US)
Pages (from-to)682-694
Number of pages13
JournalmAbs
Volume2
Issue number6
DOIs
StatePublished - Nov 1 2010

Keywords

  • Cytokine release syndrome
  • Human anti-mouse antibody
  • Immunogenicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Getts, D. R., Getts, M. T., McCarthy, D. P., Chastain, E. M. L., & Miller, S. D. (2010). Have we overestimated the benefit of human(ized) antibodies? mAbs, 2(6), 682-694. https://doi.org/10.4161/mabs.2.6.13601