Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.
Antibodies, Bispecific
/ immunology
Cell Survival
/ immunology
Coculture Techniques
Cytokines
/ biosynthesis
HEK293 Cells
Humans
Immunoglobulin G
/ immunology
Leukocytes, Mononuclear
/ immunology
MCF-7 Cells
Microscopy, Electron, Transmission
Neoplasms
/ immunology
T-Lymphocytes
/ immunology
Tumor Cells, Cultured
PBMC
T cell recruiting
TriFab
cytokine secretion
geometry
immunotherapy
Journal
Biological chemistry
ISSN: 1437-4315
Titre abrégé: Biol Chem
Pays: Germany
ID NLM: 9700112
Informations de publication
Date de publication:
25 02 2019
25 02 2019
Historique:
received:
08
08
2018
accepted:
28
11
2018
entrez:
15
2
2019
pubmed:
15
2
2019
medline:
2
11
2019
Statut:
ppublish
Résumé
A novel bispecific antibody format was applied to generate T cell-engaging antibodies. The TriFab format is a trivalent IgG-shaped entity composed of two Fab arms that bind to antigens on the surface of tumor cells, which are linked via flexible peptides to a CD3 binding moiety that replaces the CH2 domains of conventional IgGs. The distinctive feature of these T cell recruiting bispecifics is that their CD3 variable regions are incorporated between domains, rather than N- or C-terminally fused to an Fc or antibody fragments. T cell recruiting TriFabs resemble in size and shape, are expressed and show biophysical properties similar to regular IgGs. Transmission electron microscopy (TEM) demonstrates high flexibility of the cell surface binding arms as well as target antigen accessibility of the interspersed CD3 binding domain. Functional co-culturing assays of peripheral blood mononuclear cells (PBMCs) and different tumor cell lines (MCF7 and A431) revealed a dose-dependent T cell-mediated cytotoxicity that was induced by the TriFabs targeting either LeY or EGFR cell surface antigens.
Identifiants
pubmed: 30763031
doi: 10.1515/hsz-2018-0338
pii: hsz-2018-0338
doi:
Substances chimiques
Antibodies, Bispecific
0
Cytokines
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
343-350Références
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