CD47/SIRPα blocking enhances CD19/CD3-bispecific T cell engager antibody-mediated lysis of B cell malignancies.
Animals
Antibodies, Bispecific
/ pharmacology
Antigens, CD19
/ immunology
Antineoplastic Agents, Immunological
/ pharmacology
B-Lymphocytes
/ drug effects
CD3 Complex
/ immunology
CD47 Antigen
/ antagonists & inhibitors
Cell Line, Tumor
Humans
Lymphoma, Non-Hodgkin
/ drug therapy
Mice, Inbred NOD
Mice, SCID
Phagocytosis
/ drug effects
Receptors, Immunologic
/ antagonists & inhibitors
T-Lymphocytes
/ drug effects
Blinatumomab
CD47
Combination therapy
NHL
Phagocytosis
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
12 02 2019
12 02 2019
Historique:
received:
19
12
2018
accepted:
27
12
2018
pubmed:
7
1
2019
medline:
5
11
2019
entrez:
7
1
2019
Statut:
ppublish
Résumé
T cell immunotherapies are promising options in leukemia, among which the CD19/CD3-bispecific T cell engager antibody blinatumomab (MT103) has shown high response rates at very low doses in patients with lymphoma. However, the high CD47 expression in human lymphoma cells has limited the curative effects of blinatumomab other antibodies. Here we report the combined use of blinatumomab with a CD47-blocking antibody. CD47 antibodies preferentially enabled phagocytosis of non-Hodgkin lymphoma cells by both human and murine macrophages. Treatment of human non-Hodgkin lymphoma cell-engrafted mice with CD47 antibody and blinatumomab separately inhibited lymphoma partially, while combination treatment led to persistent control of lymphoma. These antibodies enhanced the therapeutic efficacy through mechanisms combining both innate and adaptive immune responses by induction of phagocytosis and T cell cytotoxicity. The combination strategy in this study might be applicable to many other cancers.
Identifiants
pubmed: 30611570
pii: S0006-291X(18)32862-6
doi: 10.1016/j.bbrc.2018.12.175
pii:
doi:
Substances chimiques
Antibodies, Bispecific
0
Antigens, CD19
0
Antineoplastic Agents, Immunological
0
CD3 Complex
0
CD47 Antigen
0
Ptpns1 protein, mouse
0
Receptors, Immunologic
0
blinatumomab
4FR53SIF3A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
739-745Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.