Heparanase-Neutralizing Monoclonal Antibody (mAb A54) Attenuates Tumor Growth and Metastasis
Abstract
1. Introduction
2. Materials and Methods
2.1. Generation of Monoclonal Antibodies (mAb)
2.2. Cells and Cell Culture
2.3. Heparanase Enzymatic Activity—ECM Degradation Assay
2.4. Matrigel Invasion Assay
2.5. Tumor Models
2.6. U87 Glioma
2.7. CAG Myeloma
2.8. MPC-11 Myeloma
2.9. Pancreatic Cancer
2.10. Crysalization of the Enzyme–Antibody Complex
2.11. Statistics
3. Results
3.1. Generation and Characterization of Heparanase-Neutralizing mAb
3.2. A54 mAb Inhibits Heparanase Enzymatic Activity, Cellular Uptake, and Cell Invasion
3.2.1. Enzymatic Activity
3.2.2. Heparanase Uptake and Processing
3.2.3. Cell Invasion
3.2.4. Anti-Heparanase A54 mAb Attenuates Myeloma and Glioma Tumor Growth
3.2.5. Combination of A54 mAb and Gemcitabine Attenuates Pancreatic Tumor Growth
3.2.6. Humanized A54 Antibody
3.2.7. Structural Features of the Interaction Between A54 and Heparanase Unravel HBD-II as the Predominant Epitope
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ECM | Extra Cellular Matrix |
FCS | Fetal Calf Serum |
kDa | Kilodalton |
HS | Heparan Sulfate |
Hpa | Heparanase |
IgG | Immunoglobulin |
IVIS | In Vivo Imaging System |
HBD | Heparin Binding Domain |
mAb | Monoclonal Antibody |
PDB | Protein Data Bank |
PBS | Phosphate-Buffered Saline |
PDAC | Pancreatic Ductal Adenocarcinoma |
PF4 | Platelet Factor 4 |
SEM | Standard Error of the Mean |
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Barash, U.; Farhoud, M.; Odeh, M.; Huberman, E.; Wu, L.; Vlodavsky, I. Heparanase-Neutralizing Monoclonal Antibody (mAb A54) Attenuates Tumor Growth and Metastasis. Cells 2025, 14, 1379. https://doi.org/10.3390/cells14171379
Barash U, Farhoud M, Odeh M, Huberman E, Wu L, Vlodavsky I. Heparanase-Neutralizing Monoclonal Antibody (mAb A54) Attenuates Tumor Growth and Metastasis. Cells. 2025; 14(17):1379. https://doi.org/10.3390/cells14171379
Chicago/Turabian StyleBarash, Uri, Malik Farhoud, Maali Odeh, Eliezer Huberman, Liang Wu, and Israel Vlodavsky. 2025. "Heparanase-Neutralizing Monoclonal Antibody (mAb A54) Attenuates Tumor Growth and Metastasis" Cells 14, no. 17: 1379. https://doi.org/10.3390/cells14171379
APA StyleBarash, U., Farhoud, M., Odeh, M., Huberman, E., Wu, L., & Vlodavsky, I. (2025). Heparanase-Neutralizing Monoclonal Antibody (mAb A54) Attenuates Tumor Growth and Metastasis. Cells, 14(17), 1379. https://doi.org/10.3390/cells14171379