Back
Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.
Journal article

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.

  • Dickopf S Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.
  • Lauer ME Roche Pharma Research and Early Development, Chemical Biology, Roche Innovation Center Basel, Grenzacherstraße 124, CH-4070 Basel, Switzerland.
  • Ringler P Center for Cellular Imaging and Nano Analytics, Biozentrum University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
  • Spick C Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.
  • Kern P Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.
  • Brinkmann U Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.
Show more…
  • 2019-02-15
Published in:
  • Biological chemistry. - 2019
PBMC
T cell recruiting
TriFab
cytokine secretion
geometry
immunotherapy
Antibodies, Bispecific
Cell Survival
Coculture Techniques
Cytokines
HEK293 Cells
Humans
Immunoglobulin G
Leukocytes, Mononuclear
MCF-7 Cells
Microscopy, Electron, Transmission
Neoplasms
T-Lymphocytes
Tumor Cells, Cultured
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/232487
Statistics
Document views: 39 File downloads: