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<p>Pritumumab is a human IgG1 kappa antibody that targets ecto-domain vimentin (EDV) which is overexpressed in several malignant tumors including glioblastomas. To understand preclinical biological activity and safety of pritumumab derived from Chinese hamster ovary (CHO) cells, we evaluated tumor targeting ability, brain-tumor barrier permeability, growth inhibition, and primate safety studies. In-vivo and ex-vivo imaging studies demonstrate pritumumab to cross the blood brain/blood tumor barrier and an <sup>89</sup>Zr-labeled pritumumab immunoconjugate showed the antibody specifically targeted tumor cells. In mouse xenograft models, pritumumab inhibited the growth of U251 glioblastoma and PANC-1 pancreatic cancer cells. A 29-day intravenous toxicology study in cynomolgus monkeys was carried out to analyze the safety and toxicity of pritumumab, and no toxic effects were observed. Overall, these data together suggest pritumumab is biologically active and animal models can be used to further understand the various functions of the antibody. Clinical trials in brain cancer patients assessing safety and efficacy of pritumumab as a therapeutic for brain cancer are in process.</p>

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Characterization of pritumumab in murine models and primate safety study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月25日

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  • Avani A. Mody,
  • Rajesh Mukthavaram,
  • Pengfei Jiang,
  • Kishore Gangangari,
  • Nagavarakishore Pillarsetty,
  • Pranav R. Kesari,
  • Vijay Padul,
  • Sneha L. Kesari,
  • Elnaz Rahbarlayegh,
  • Mark C. Glassy,
  • Santosh Kesari

摘要

Pritumumab is a human IgG1 kappa antibody that targets ecto-domain vimentin (EDV) which is overexpressed in several malignant tumors including glioblastomas. To understand preclinical biological activity and safety of pritumumab derived from Chinese hamster ovary (CHO) cells, we evaluated tumor targeting ability, brain-tumor barrier permeability, growth inhibition, and primate safety studies. In-vivo and ex-vivo imaging studies demonstrate pritumumab to cross the blood brain/blood tumor barrier and an 89Zr-labeled pritumumab immunoconjugate showed the antibody specifically targeted tumor cells. In mouse xenograft models, pritumumab inhibited the growth of U251 glioblastoma and PANC-1 pancreatic cancer cells. A 29-day intravenous toxicology study in cynomolgus monkeys was carried out to analyze the safety and toxicity of pritumumab, and no toxic effects were observed. Overall, these data together suggest pritumumab is biologically active and animal models can be used to further understand the various functions of the antibody. Clinical trials in brain cancer patients assessing safety and efficacy of pritumumab as a therapeutic for brain cancer are in process.