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Published on: September 16, 2019
Pharmacokinetics, Biodistribution, and Toxicity Evaluation of Anti-SEMA3A (F11) in In Vivo Models
Jaehyun Lee1,2, Donggeon Kim2, Eunju Son2
1Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
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.
Insights
The F11 antibody targeting semaphorin 3A demonstrated significant anti-angiogenic and tumor-inhibitory effects in glioblastoma models. Its pharmacokinetic and biodistribution profiles support potential clinical applications.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Investigating the therapeutic potential of antibodies targeting specific molecular pathways in cancer.
- Understanding the role of semaphorin 3A in tumor progression and angiogenesis.
Purpose of the Study:
- To evaluate the pharmacokinetics (PK), tissue distribution, and toxicity of the F11 antibody against semaphorin 3A.
- To explore the anti-angiogenic and tumor-inhibitory effects of F11 in preclinical models.
Main Methods:
- Establishment of patient-derived xenograft (PDX) models using glioblastoma multiforme (GBM) cells.
- Treatment of GBM PDX models with the F11 antibody.
- Analysis of tumor growth, angiogenesis, PK, and tissue distribution.
Main Results:
- F11 significantly reduced tumor growth and angiogenesis in GBM PDX models.
- Linear pharmacokinetics were observed for F11 in serum, with a clearance of 4.63–7.12 ml/d/kg and a half-life of 6.9–9.4 days.
- F11 exhibited expected tissue distribution in kidney, liver, and heart, with notable presence in the brain.
Conclusions:
- The F11 antibody displays significant anti-angiogenic and tumor-inhibitory properties.
- Pharmacokinetic and biodistribution data suggest F11's potential for clinical development in cancer therapy.
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