A Cross-Species Reactive TIGIT-Blocking Antibody Fc Dependently Confers Potent Antitumor Effects.
Animals
Antibodies, Blocking
/ immunology
Antibodies, Neoplasm
/ immunology
Antineoplastic Agents, Immunological
/ immunology
Female
Humans
Immunoglobulin Fc Fragments
/ immunology
Jurkat Cells
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Proteins
/ antagonists & inhibitors
Neoplasms, Experimental
/ drug therapy
Receptors, Immunologic
/ antagonists & inhibitors
Xenograft Model Antitumor Assays
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
26
11
2019
accepted:
08
08
2020
pubmed:
6
9
2020
medline:
30
3
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
The T cell immunoreceptor with Ig and ITIM domains (TIGIT) has been shown to exert inhibitory roles in antitumor immune responses. In this study, we report the development of a human mAb, T4, which recognizes both human and mouse TIGIT and blocks the interaction of TIGIT with its ligand CD155 in both species. The T4 Ab targets the segment connecting F and G strands of TIGIT's extracellular IgV domain, and we show in studies with mouse tumor models that the T4 Ab exerts strong antitumor activity and induces durable immune memory against various tumor types. Mechanistically, we demonstrate that the T4 Ab's antitumor effects are mediated via multiple immunological impacts, including a CD8
Identifiants
pubmed: 32887749
pii: jimmunol.1901413
doi: 10.4049/jimmunol.1901413
doi:
Substances chimiques
Antibodies, Blocking
0
Antibodies, Neoplasm
0
Antineoplastic Agents, Immunological
0
Immunoglobulin Fc Fragments
0
Neoplasm Proteins
0
Receptors, Immunologic
0
TIGIT protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2156-2168Informations de copyright
Copyright © 2020 by The American Association of Immunologists, Inc.