Engineering the Human Fc Region Enables Direct Cell Killing by Cancer Glycan-Targeting Antibodies without the Need for Immune Effector Cells or Complement.
Animals
Antibodies, Monoclonal
/ immunology
Antibody Affinity
/ immunology
Antibody-Dependent Cell Cytotoxicity
Cell Death
/ immunology
Cell Line, Tumor
Colorectal Neoplasms
/ immunology
Complement System Proteins
Female
Genetic Engineering
Humans
Immunoglobulin Fc Fragments
/ immunology
Immunoglobulin G
/ immunology
Immunotherapy
Mice
Mice, Inbred BALB C
Mice, Nude
Polysaccharides
/ immunology
Random Allocation
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
21
11
2019
revised:
25
03
2020
accepted:
05
06
2020
pubmed:
14
6
2020
medline:
29
12
2020
entrez:
14
6
2020
Statut:
ppublish
Résumé
Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to noncovalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization. Using the Lewis
Identifiants
pubmed: 32532823
pii: 0008-5472.CAN-19-3599
doi: 10.1158/0008-5472.CAN-19-3599
pmc: PMC7611157
mid: EMS128574
doi:
Substances chimiques
Antibodies, Monoclonal
0
Immunoglobulin Fc Fragments
0
Immunoglobulin G
0
Polysaccharides
0
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3399-3412Subventions
Organisme : Medical Research Council
ID : MR/M015564/1
Pays : United Kingdom
Informations de copyright
©2020 American Association for Cancer Research.
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