Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer.

Antigens, CD19 / immunology GPI-Linked Proteins / antagonists & inhibitors Humans Immunotherapy, Adoptive / adverse effects Lymphocyte Depletion / methods Mesothelin Neoplasm Metastasis Neoplasm Staging Pancreatic Neoplasms / immunology Pilot Projects Receptors, Chimeric Antigen / immunology T-Lymphocytes / immunology Treatment Outcome
B cells CD19 chimeric antigen receptor mesothelin pancreatic cancer

Journal

Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581

Informations de publication

Date de publication:
04 11 2020
Historique:
received: 14 05 2020
revised: 12 06 2020
accepted: 10 07 2020
pubmed: 31 7 2020
medline: 12 8 2021
entrez: 31 7 2020
Statut: ppublish

Résumé

B cells infiltrate pancreatic ductal adenocarcinoma (PDAC) and in preclinical cancer models, can suppress T cell immunosurveillance in cancer. Here, we conducted a pilot study to assess the safety and feasibility of administering lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin to target tumor cells along with CART cells redirected against CD19 to deplete B cells. Both CARs contained 4-1BB and CD3ζ signaling domains. Three patients with chemotherapy-refractory PDAC received 1.5 g/m

Identifiants

DOI: 10.1016/j.ymthe.2020.07.017 PMID: 32730744 PMC: PMC7647666
pubmed: 32730744
pii: S1525-0016(20)30368-3
doi: 10.1016/j.ymthe.2020.07.017
pmc: PMC7647666
pii:
doi:

Substances chimiques

Antigens, CD19 0
GPI-Linked Proteins 0
Receptors, Chimeric Antigen 0
Mesothelin J27WDC343N

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2367-2378

Subventions

Organisme : NCI NIH HHS
ID : R01 CA197916
Pays : United States

Informations de copyright

Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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Auteurs

Andrew H Ko (AH)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Alexander C Jordan (AC)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Evan Tooker (E)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Simon F Lacey (SF)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.

Renee B Chang (RB)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Yan Li (Y)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Alan P Venook (AP)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Margaret Tempero (M)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Lloyd Damon (L)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Lawrence Fong (L)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Mark H O'Hara (MH)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Bruce L Levine (BL)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.

J Joseph Melenhorst (JJ)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gabriela Plesa (G)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.

Carl H June (CH)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gregory L Beatty (GL)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: gregory.beatty@uphs.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes B › Antigènes CD19 › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunisation passive › Transfert adoptif › Immunothérapie adoptive › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunosuppression thérapeutique › Déplétion lymphocytaire › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Mésothéline › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Diagnostic › Pronostic › Stadification tumorale › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Projets pilotes › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs chimériques pour l'antigène › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Dual Targeting of Mesothelin and CD19 with...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Dual Targeting of Mesothelin and CD19 with...