Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells.

Animals B7 Antigens / genetics B7-H1 Antigen / immunology CD28 Antigens / immunology Carcinoma, Pancreatic Ductal / genetics Cell Line, Tumor Coculture Techniques Female Humans Immunotherapy, Adoptive / adverse effects Male Mice, Inbred C57BL Neuroblastoma / genetics Ovarian Neoplasms / genetics Pancreatic Neoplasms / genetics Receptors, Chimeric Antigen / genetics Signal Transduction Tumor Burden Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology Xenograft Model Antitumor Assays
4-1BB B7-H3 CD28 PD-1/PD-L1 chimerc antigen receptor neuroblastoma ovarian cancer pancreatic cancer solid tumors

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
11 02 2019
Historique:
received: 17 10 2017
revised: 31 10 2018
accepted: 02 01 2019
entrez: 13 2 2019
pubmed: 13 2 2019
medline: 18 12 2019
Statut: ppublish

Résumé

The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3.CAR-Ts, and superior antitumor activity when targeting tumor cells that constitutively expressed PD-L1. We took advantage of the cross-reactivity of the B7-H3.CAR with murine B7-H3, and found that B7-H3.CAR-Ts significantly controlled tumor growth in a syngeneic tumor model without evident toxicity. These findings support the clinical development of B7-H3.CAR-Ts.

Identifiants

DOI: 10.1016/j.ccell.2019.01.002 PMID: 30753824 PMC: PMC6645919
pubmed: 30753824
pii: S1535-6108(19)30002-9
doi: 10.1016/j.ccell.2019.01.002
pmc: PMC6645919
mid: NIHMS1035462
pii:
doi:

Substances chimiques

B7 Antigens 0
B7-H1 Antigen 0
CD274 protein, human 0
CD276 protein, human 0
CD28 Antigens 0
Cd274 protein, mouse 0
Cd276 protein, mouse 0
Receptors, Chimeric Antigen 0
TNFRSF9 protein, human 0
Tnfrsf9 protein, mouse 0
Tumor Necrosis Factor Receptor Superfamily, Member 9 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

221-237.e8

Subventions

Organisme : NCI NIH HHS
ID : R01 CA193140
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA231766
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA199064
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA223886
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028172
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA071341
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Hongwei Du (H)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Koichi Hirabayashi (K)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Sarah Ahn (S)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.

Nancy Porterfield Kren (NP)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.

Stephanie Ann Montgomery (SA)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.

Xinhui Wang (X)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Karthik Tiruthani (K)

Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.

Bhalchandra Mirlekar (B)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.

Daniel Michaud (D)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA.

Kevin Greene (K)

Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.

Silvia Gabriela Herrera (SG)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Yang Xu (Y)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Chuang Sun (C)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Yuhui Chen (Y)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Xingcong Ma (X)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Cristina Rosa Ferrone (CR)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Yuliya Pylayeva-Gupta (Y)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.

Jen Jen Yeh (JJ)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Surgery, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.

Rihe Liu (R)

Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA; Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.

Barbara Savoldo (B)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA.

Soldano Ferrone (S)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Gianpietro Dotti (G)

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: gdotti@med.unc.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD274 › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigène CD28 › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de coculture › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunisation passive › Transfert adoptif › Immunothérapie adoptive › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Tumeurs neuroectodermiques primitives périphériques › Neuroblastome › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs chimériques pour l'antigène › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Techniques d'investigation › Charge tumorale › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux facteurs de nécrose tumorale › Antigènes CD137 › Antitumor Responses in the Absence of Toxicity...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Antitumor Responses in the Absence of Toxicity...