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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yun Jung Kim, Eun Mi Koh, Chi Hun Song, Mi Sun Byun, Yu Ri Choi, Eun-Jeong Jeon, Kyunghwa Hwang, Sang Kyum Kim, Sang In Yang, Kyung Jin Jung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e7e1b8db8614df985eda9ab5846fc92
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1e7e1b8db8614df985eda9ab5846fc92
record_format	dspace
spelling	oai:doaj.org-article:1e7e1b8db8614df985eda9ab5846fc922021-12-02T17:52:40ZPreclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models10.1038/s41598-021-91360-72045-2322https://doaj.org/article/1e7e1b8db8614df985eda9ab5846fc922021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91360-7https://doaj.org/toc/2045-2322Abstract 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 profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.Yun Jung KimEun Mi KohChi Hun SongMi Sun ByunYu Ri ChoiEun-Jeong JeonKyunghwa HwangSang Kyum KimSang In YangKyung Jin JungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yun Jung Kim Eun Mi Koh Chi Hun Song Mi Sun Byun Yu Ri Choi Eun-Jeong Jeon Kyunghwa Hwang Sang Kyum Kim Sang In Yang Kyung Jin Jung Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
description	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 profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.
format	article
author	Yun Jung Kim Eun Mi Koh Chi Hun Song Mi Sun Byun Yu Ri Choi Eun-Jeong Jeon Kyunghwa Hwang Sang Kyum Kim Sang In Yang Kyung Jin Jung
author_facet	Yun Jung Kim Eun Mi Koh Chi Hun Song Mi Sun Byun Yu Ri Choi Eun-Jeong Jeon Kyunghwa Hwang Sang Kyum Kim Sang In Yang Kyung Jin Jung
author_sort	Yun Jung Kim
title	Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
title_short	Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
title_full	Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
title_fullStr	Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
title_full_unstemmed	Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
title_sort	preclinical immunogenicity testing using anti-drug antibody analysis of gx-g3, fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1e7e1b8db8614df985eda9ab5846fc92
work_keys_str_mv	AT yunjungkim preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT eunmikoh preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT chihunsong preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT misunbyun preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT yurichoi preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT eunjeongjeon preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT kyunghwahwang preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT sangkyumkim preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT sanginyang preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels AT kyungjinjung preclinicalimmunogenicitytestingusingantidrugantibodyanalysisofgxg3fcfusedrecombinanthumangranulocytecolonystimulatingfactorinratandmonkeymodels
_version_	1718379155584712704

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

Ejemplares similares