Pharmacokinetics, biodistribution, and toxicity evaluation of Anti-SEMA3A (F11) in in vivo models

Jaehyun Lee; Donggeon Kim; Eunju Son; Su Ji Yoo; Jason K. Sa; Yong Jae Shin; Yeup Yoon; Do Hyun Nam

doi:10.21873/anticanres.12524

Pharmacokinetics, biodistribution, and toxicity evaluation of Anti-SEMA3A (F11) in in vivo models

Jaehyun Lee, Donggeon Kim, Eunju Son, Su Ji Yoo, Jason K. Sa, Yong Jae Shin, Yeup Yoon, Do Hyun Nam

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background/Aim: The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. Materials and Methods: Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. Results: F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model. Within the range of administered doses, the PK of F11 in serum demonstrated a linear fashion, consistent with general PK profiles of soluble antigen-targeting antibodies. Additionally, the clearance level was detected at between 4.63 and 7.12 ml/d/kg, while the biological half-life was measured at 6.9 and 9.4 days. Tissue distribution of F11 in kidney, liver and heart was consistent with previously reported antibody patterns. However, the presence of F11 in the brain was an interesting finding. Conclusion: Collectively, our results revealed angiogenic and tumor-inhibitory effect of F11 antibody and its potential therapeutic use within a clinical framework based on PK, biodistribution and toxicity evaluation in mouse models.

Original language	English
Pages (from-to)	2803-2810
Number of pages	8
Journal	Anticancer research
Volume	38
Issue number	5
DOIs	https://doi.org/10.21873/anticanres.12524
Publication status	Published - 2018 May
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. (HI14C3418). The biospecimens for this study were provided by Samsung Medical Center BioBank.

Publisher Copyright:
© 2018 International Institute of Anticancer Research. All rights reserved.

Keywords

Fully human antibody
Pharmacokinetics
SEMA3A
Semaphorin3A
Tissue distribution
Toxicity

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.12524

Cite this

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title = "Pharmacokinetics, biodistribution, and toxicity evaluation of Anti-SEMA3A (F11) in in vivo models",

abstract = "Background/Aim: The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. Materials and Methods: Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. Results: F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model. Within the range of administered doses, the PK of F11 in serum demonstrated a linear fashion, consistent with general PK profiles of soluble antigen-targeting antibodies. Additionally, the clearance level was detected at between 4.63 and 7.12 ml/d/kg, while the biological half-life was measured at 6.9 and 9.4 days. Tissue distribution of F11 in kidney, liver and heart was consistent with previously reported antibody patterns. However, the presence of F11 in the brain was an interesting finding. Conclusion: Collectively, our results revealed angiogenic and tumor-inhibitory effect of F11 antibody and its potential therapeutic use within a clinical framework based on PK, biodistribution and toxicity evaluation in mouse models.",

keywords = "Fully human antibody, Pharmacokinetics, SEMA3A, Semaphorin3A, Tissue distribution, Toxicity",

author = "Jaehyun Lee and Donggeon Kim and Eunju Son and Yoo, {Su Ji} and Sa, {Jason K.} and Shin, {Yong Jae} and Yeup Yoon and Nam, {Do Hyun}",

note = "Funding Information: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. (HI14C3418). The biospecimens for this study were provided by Samsung Medical Center BioBank. Publisher Copyright: {\textcopyright} 2018 International Institute of Anticancer Research. All rights reserved.",

year = "2018",

month = may,

doi = "10.21873/anticanres.12524",

language = "English",

volume = "38",

pages = "2803--2810",

journal = "Anticancer research",

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T1 - Pharmacokinetics, biodistribution, and toxicity evaluation of Anti-SEMA3A (F11) in in vivo models

AU - Lee, Jaehyun

AU - Kim, Donggeon

AU - Son, Eunju

AU - Yoo, Su Ji

AU - Sa, Jason K.

AU - Shin, Yong Jae

AU - Yoon, Yeup

AU - Nam, Do Hyun

N1 - Funding Information: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. (HI14C3418). The biospecimens for this study were provided by Samsung Medical Center BioBank. Publisher Copyright: © 2018 International Institute of Anticancer Research. All rights reserved.

PY - 2018/5

Y1 - 2018/5

N2 - Background/Aim: The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. Materials and Methods: Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. Results: F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model. Within the range of administered doses, the PK of F11 in serum demonstrated a linear fashion, consistent with general PK profiles of soluble antigen-targeting antibodies. Additionally, the clearance level was detected at between 4.63 and 7.12 ml/d/kg, while the biological half-life was measured at 6.9 and 9.4 days. Tissue distribution of F11 in kidney, liver and heart was consistent with previously reported antibody patterns. However, the presence of F11 in the brain was an interesting finding. Conclusion: Collectively, our results revealed angiogenic and tumor-inhibitory effect of F11 antibody and its potential therapeutic use within a clinical framework based on PK, biodistribution and toxicity evaluation in mouse models.

AB - Background/Aim: The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. Materials and Methods: Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. Results: F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model. Within the range of administered doses, the PK of F11 in serum demonstrated a linear fashion, consistent with general PK profiles of soluble antigen-targeting antibodies. Additionally, the clearance level was detected at between 4.63 and 7.12 ml/d/kg, while the biological half-life was measured at 6.9 and 9.4 days. Tissue distribution of F11 in kidney, liver and heart was consistent with previously reported antibody patterns. However, the presence of F11 in the brain was an interesting finding. Conclusion: Collectively, our results revealed angiogenic and tumor-inhibitory effect of F11 antibody and its potential therapeutic use within a clinical framework based on PK, biodistribution and toxicity evaluation in mouse models.

KW - Fully human antibody

KW - Pharmacokinetics

KW - SEMA3A

KW - Semaphorin3A

KW - Tissue distribution

KW - Toxicity

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SN - 0250-7005

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EP - 2810

JO - Anticancer research

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ER -

Pharmacokinetics, biodistribution, and toxicity evaluation of Anti-SEMA3A (F11) in in vivo models

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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