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

Kim, Yun Jung; Koh, Eun Mi; Song, Chi Hun; Byun, Mi Sun; Choi, Yu Ri; Jeon, Eun-Jeong; Hwang, Kyunghwa; Kim, Sang Kyum; Yang, Sang In; Jung, Kyung Jin

doi:10.1038/s41598-021-91360-7

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

Scientific reports, v.11 no.1, 2021년, pp.12004 -

Kim, Yun Jung (Genexine, Inc, Korea Bio Park, Seongnam, 13488 Republic of Korea) , Koh, Eun Mi (Bioanalytical and Immunoanalytical Research Group, Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea) , Song, Chi Hun (Bioanalytical and Immunoanalytical Research Group, Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea) , Byun, Mi Sun (Genexine, Inc, Korea Bio Park, Seongnam, 13488 Republic of Korea) , Choi, Yu Ri (Genexine, Inc, Korea Bio Park, Seongnam, 13488 Republic of Korea) , Jeon, Eun-Jeong (Bioanalytical and Immunoanalytical Research Group, Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea) , Hwang, Kyunghwa (Jeonbuk Analytical Research Group, In Vivo Hazard Evaluation and Research Division, Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeongeup, Jeollabuk-do 56212 Republic of Korea) , Kim, Sang Kyum (College of Pharmacy, Chungnam National Uni) , Yang, Sang In , Jung, Kyung Jin

Abstract ▼ AI-Helper

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.

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