alexa Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate.
Immunology

Immunology

Immunotherapy: Open Access

Author(s): Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J

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PURPOSE: An antibody-drug conjugate consisting of monomethyl auristatin E (MMAE) conjugated to the anti-CD30 monoclonal antibody (mAb) cAC10, with eight drug moieties per mAb, was previously shown to have potent cytotoxic activity against CD30(+) malignant cells. To determine the effect of drug loading on antibody-drug conjugate therapeutic potential, we assessed cAC10 antibody-drug conjugates containing different drug-mAb ratios in vitro and in vivo. EXPERIMENTAL DESIGN: Coupling MMAE to the cysteines that comprise the interchain disulfides of cAC10 created an antibody-drug conjugate population, which was purified using hydrophobic interaction chromatography to yield antibody-drug conjugates with two, four, and eight drugs per antibody (E2, E4, and E8, respectively). Antibody-drug conjugate potency was tested in vitro against CD30(+) lines followed by in vivo xenograft models. The maximum-tolerated dose and pharmacokinetic profiles of the antibody-drug conjugates were investigated in mice. RESULTS: Although antibody-drug conjugate potency in vitro was directly dependent on drug loading (IC(50) values E8
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  • DOI: 10.1158/1078-0432.CCR-04-0789
  • Open Access
  • This article was published in Clin Cancer Res and referenced in Immunotherapy: Open Access

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