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Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
by
Bujak, Emil
, Pretto, Francesca
, Neri, Dario
in
Animals
/ Antibodies, Monoclonal - pharmacology
/ Antigens
/ Apoptosis
/ Biodistribution
/ Biological products
/ Blood vessels
/ Cancer
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Chromatography
/ Clinical trials
/ Glycoproteins
/ Humans
/ Leukocytes
/ Medicine
/ Medicine & Public Health
/ Mice, Inbred C3H
/ Mice, Inbred C57BL
/ Mice, Nude
/ Molecular Targeted Therapy
/ Monoclonal antibodies
/ Neoplasms, Experimental - metabolism
/ Oncology
/ Pharmacology/Toxicology
/ Phospholipids - metabolism
/ Preclinical Studies
/ Proteins
/ Sodium
/ Studies
/ Tumors
/ Vascular endothelial growth factor
2015
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Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
by
Bujak, Emil
, Pretto, Francesca
, Neri, Dario
in
Animals
/ Antibodies, Monoclonal - pharmacology
/ Antigens
/ Apoptosis
/ Biodistribution
/ Biological products
/ Blood vessels
/ Cancer
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Chromatography
/ Clinical trials
/ Glycoproteins
/ Humans
/ Leukocytes
/ Medicine
/ Medicine & Public Health
/ Mice, Inbred C3H
/ Mice, Inbred C57BL
/ Mice, Nude
/ Molecular Targeted Therapy
/ Monoclonal antibodies
/ Neoplasms, Experimental - metabolism
/ Oncology
/ Pharmacology/Toxicology
/ Phospholipids - metabolism
/ Preclinical Studies
/ Proteins
/ Sodium
/ Studies
/ Tumors
/ Vascular endothelial growth factor
2015
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Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
by
Bujak, Emil
, Pretto, Francesca
, Neri, Dario
in
Animals
/ Antibodies, Monoclonal - pharmacology
/ Antigens
/ Apoptosis
/ Biodistribution
/ Biological products
/ Blood vessels
/ Cancer
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Chromatography
/ Clinical trials
/ Glycoproteins
/ Humans
/ Leukocytes
/ Medicine
/ Medicine & Public Health
/ Mice, Inbred C3H
/ Mice, Inbred C57BL
/ Mice, Nude
/ Molecular Targeted Therapy
/ Monoclonal antibodies
/ Neoplasms, Experimental - metabolism
/ Oncology
/ Pharmacology/Toxicology
/ Phospholipids - metabolism
/ Preclinical Studies
/ Proteins
/ Sodium
/ Studies
/ Tumors
/ Vascular endothelial growth factor
2015
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Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
Journal Article
Generation and tumor recognition properties of two human monoclonal antibodies specific to cell surface anionic phospholipids
2015
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Overview
Summary
Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on the surface of proliferating endothelial cells, tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage biopharmaceuticals. One of these products (bavituximab) is currently being investigated in Phase 3 clinical trials. There are conflicting reports on the ability of bavituximab and other antibodies to recognize PS directly or through beta-2 glycoprotein 1, a serum protein that is not highly conserved across species. Here, we report on the generation and characterization of two fully human antibodies directed against phosphatidylserine. One of these antibodies (PS72) bound specifically to phosphatidylserine and to phosphatidic acid, but did not recognize other closely related phospholipids, while the other antibody (PS41) also bound to cardiolipin. Both PS72 and PS41 stained 8/9 experimental tumor models in vitro, but both antibodies failed to exhibit a preferential tumor accumulation in vivo, as revealed by quantitative biodistribution analysis. Our findings indicate that anionic phospholipids are exposed and accessible in most tumor types, but cast doubts about the possibility of efficiently targeting tumors in vivo with PS-specific reagents.
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