Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models.

Scientific Reports
Yun Jung KimKyung Jin Jung

Abstract

Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic prof...Continue Reading

References

Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A M CohenL M Souza
Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·V Trillet-LenoirD Tomita
Jan 4, 2001·Journal of the National Cancer Institute·R García-CarboneroL Paz-Ares
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E E IdusogieM G Mulkerrin
Sep 30, 2008·Journal of the Neurological Sciences·Bruce A CohenGavin Giovannoni
Nov 11, 2008·Journal of Pharmaceutical and Biomedical Analysis·Gopi ShankarEugen Koren
Apr 7, 2009·Regulatory Toxicology and Pharmacology : RTP·Rafael PonceDan Wierda
Aug 27, 2010·Journal of Pharmaceutical Sciences·Satish Kumar Singh
Nov 12, 2010·Annals of the Rheumatic Diseases·Anna JamnitskiGerrit Jan Wolbink
Jul 28, 2012·EMBO Molecular Medicine·Daniel M CzajkowskyRichard J Pleass
Sep 27, 2012·Protein Expression and Purification·Jung-Hwan LeeChang-Shin Park
Aug 8, 2013·Journal of Immunotoxicology·Kirsty D RatanjiIan Kimber

❮ Previous
Next ❯

Software Mentioned

WinNonlin®
it®
Analyse
SPSS
ARRIVE

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Naoki Wakimoto, K Motoyoshi
Nihon rinsho. Japanese journal of clinical medicine
Naoki Wakimoto
Nihon rinsho. Japanese journal of clinical medicine
Naoki Wakimoto, K Motoyoshi
Nihon rinsho. Japanese journal of clinical medicine
Naoki Wakimoto
© 2021 Meta ULC. All rights reserved