Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma.
Animals
Brain
/ diagnostic imaging
Brain Neoplasms
/ diagnostic imaging
Cell Line, Tumor
/ transplantation
Disease Models, Animal
ErbB Receptors
/ immunology
Female
Glioblastoma
/ diagnostic imaging
Humans
Immunoconjugates
/ administration & dosage
Immunoglobulin Fc Fragments
/ administration & dosage
Immunotherapy, Adoptive
/ methods
Injections, Intralesional
/ methods
Interleukin-12
/ administration & dosage
Magnetic Resonance Imaging, Interventional
Mice
Receptors, Chimeric Antigen
/ immunology
Single-Chain Antibodies
/ administration & dosage
T-Lymphocytes, Regulatory
/ immunology
Tumor Microenvironment
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 01 2021
19 01 2021
Historique:
received:
08
03
2020
accepted:
11
12
2020
entrez:
20
1
2021
pubmed:
21
1
2021
medline:
2
2
2021
Statut:
epublish
Résumé
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4
Identifiants
pubmed: 33469002
doi: 10.1038/s41467-020-20599-x
pii: 10.1038/s41467-020-20599-x
pmc: PMC7815781
doi:
Substances chimiques
Immunoconjugates
0
Immunoglobulin Fc Fragments
0
Receptors, Chimeric Antigen
0
Single-Chain Antibodies
0
epidermal growth factor receptor VIII
0
Interleukin-12
187348-17-0
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
444Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C36463/A20764
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C22442/A20766
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C36463/A22246
Pays : United Kingdom
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