Characterization of pritumumab in murine models and primate safety study.

in Scientific reports by 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

TLDR

  • Pritumumab, a human IgG1 kappa antibody targeting ecto-domain vimentin (EDV), demonstrated biological activity and safety in preclinical studies, inhibiting tumor growth and crossing the blood brain/blood tumor barrier.
  • Clinical trials are underway to assess the safety and efficacy of pritumumab as a therapeutic for brain cancer, building on its promising preclinical profile.

Abstract

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 anZr-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.

Overview

  • The main focus of the study is to evaluate the preclinical biological activity and safety of pritumumab, a human IgG1 kappa antibody that targets ecto-domain vimentin (EDV) in several malignant tumors, including glioblastomas.
  • The study used in-vivo and ex-vivo imaging studies, tumor targeting ability, brain-tumor barrier permeability, growth inhibition, and primate safety studies to assess pritumumab's biological activity and safety.
  • The primary objective of the study is to understand the preclinical profile of pritumumab and its potential as a therapeutic for brain cancer, with clinical trials in brain cancer patients currently underway.

Comparative Analysis & Findings

  • In-vivo and ex-vivo imaging studies showed that pritumumab crossed the blood brain/blood tumor barrier and anZr-labeled pritumumab immunoconjugate 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 showed no toxic effects of pritumumab, indicating its safety and bioavailability.

Implications and Future Directions

  • The findings suggest that pritumumab is a promising therapeutic agent for brain cancer treatment and warrants further investigation in clinical trials.
  • Future studies can build on these results to further understand the mechanisms of action and efficacy of pritumumab in brain cancer patients.
  • The study highlights the potential of pritumumab to improve treatment outcomes for glioblastoma patients and encourages the exploration of its use in combination with other therapies.
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