An antibody fragment against human delta-like ligand-4 for inhibition of cell proliferation and neovascularization.

Abstract

OBJECTIVES:

Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor.

MATERIALS AND METHODS:

In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays.

RESULTS:

Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM.

CONCLUSIONS:

These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.

• Authors: Rasoul Baharlou, Nader Tajik, Mahdi Behdani, Mohammad Ali Shokrgozar, Vajiheh Tavana, Fatemeh Kazemi-Lomedasht, Fatemeh Faraji, Mahdi Habibi-Anbouhi
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 40 Issue 5 Pg. 368-374 (Oct 2018) ISSN: 1532-2513 [Electronic] England
• PMID: 30183441 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Immunoglobulin Fragments
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• delta protein

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (drug effects)
• HEK293 Cells
• Humans
• Immunoglobulin Fragments (pharmacology)
• Intracellular Signaling Peptides and Proteins (immunology)
• Membrane Proteins (immunology)
• Neovascularization, Pathologic (drug therapy)