Antagonism of IAPs Enhances CAR T-cell Efficacy.

Animals Apoptosis Cell Line, Tumor Cytokines / metabolism Disease Models, Animal Humans Immunotherapy, Adoptive Inhibitor of Apoptosis Proteins / antagonists & inhibitors Mice Neoplasms / etiology Receptors, Antigen, T-Cell / genetics Receptors, Chimeric Antigen / genetics T-Lymphocytes / immunology

Journal

Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637

Informations de publication

Date de publication:
02 2019
Historique:
received: 26 06 2018
revised: 06 10 2018
accepted: 10 01 2019
pubmed: 18 1 2019
medline: 9 4 2020
entrez: 18 1 2019
Statut: ppublish

Résumé

Chimeric antigen receptor (CAR) T-cell therapy has proven successful in the treatment of hematological malignancies, notably acute lymphoblastic leukemia and B-cell lymphoma. However, the efficacy of CAR T cells against solid tumors is poor, likely due to tumor-associated immunosuppression. Here, we demonstrated that antagonizing the "inhibitor of apoptosis proteins" with the clinical smac-mimetic, birinapant, significantly enhanced the antitumor activity of CAR T cells in a tumor necrosis factor (TNF)-dependent manner. Enhanced tumor cell death occurred independently of the perforin-mediated granule exocytosis pathway, underscoring the cytotoxic potential of CAR T-cell-derived TNF. Combining CAR T-cell therapy with birinapant significantly reduced established tumor growth

Identifiants

DOI: 10.1158/2326-6066.CIR-18-0428 PMID: 30651288
pubmed: 30651288
pii: 2326-6066.CIR-18-0428
doi: 10.1158/2326-6066.CIR-18-0428
doi:

Substances chimiques

Cytokines 0
Inhibitor of Apoptosis Proteins 0
Receptors, Antigen, T-Cell 0
Receptors, Chimeric Antigen 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

183-192

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Jessica Michie (J)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Paul A Beavis (PA)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Andrew J Freeman (AJ)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
ORCID: 0000-0003-0040-5617

Stephin J Vervoort (SJ)

Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Kelly M Ramsbottom (KM)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Vignesh Narasimhan (V)

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Gastrointestinal Cancer Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
ORCID: 0000-0002-8964-3082

Emily J Lelliott (EJ)

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Cancer Therapeutics Program, Peter MaCallum Cancer Centre, Melbourne, Victoria, Australia.

Najoua Lalaoui (N)

Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.
ORCID: 0000-0002-0165-3324

Robert G Ramsay (RG)

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Gastrointestinal Cancer Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
ORCID: 0000-0001-5003-0433

Ricky W Johnstone (RW)

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Translational Haematology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

John Silke (J)

Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
ORCID: 0000-0002-7611-5774

Phillip K Darcy (PK)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Ilia Voskoboinik (I)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Conor J Kearney (CJ)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Jane Oliaro (J)

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. jane.oliaro@petermac.org.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunisation passive › Transfert adoptif › Immunothérapie adoptive › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Protéines IAP › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Tumeurs › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs chimériques pour l'antigène › Antagonism of IAPs Enhances CAR T-cell Efficacy.
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Antagonism of IAPs Enhances CAR T-cell Efficacy.