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Anticancer Res. 2018 May;38(5):2803-2810.

Pharmacokinetics, Biodistribution, and Toxicity Evaluation of Anti-SEMA3A (F11) in In Vivo Models.

Lee J1,2, Kim D2, Son E2, Yoo SJ2, Sa JK2, Shin YJ2, Yoon Y3,2, Nam DH3,2,4.

Author information

1
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
2
Institute for Refractory Cancer Research, Research institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.
3
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea nsnam@skku.edu benedict.yoon@samsung.com.
4
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

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:

SEMA3A; Semaphorin3A; fully human antibody; pharmacokinetics; tissue distribution; toxicity

PMID:
29715102
DOI:
10.21873/anticanres.12524
[Indexed for MEDLINE]

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