ERBB2-CAR-Engineered Cytokine-Induced Killer Cells Exhibit Both CAR-Mediated and Innate Immunity Against High-Risk Rhabdomyosarcoma.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2020
Historique:
received: 08 07 2020
accepted: 07 09 2020
entrez: 16 11 2020
pubmed: 17 11 2020
medline: 23 6 2021
Statut: epublish

Résumé

High-risk rhabdomyosarcoma (RMS) occurring in childhood to young adulthood is associated with a poor prognosis; especially children above the age of 10 with advanced stage alveolar RMS still succumb to the disease within a median of 2 years. The advent of chimeric antigen receptor (CAR)-engineered T cells marked significant progress in the treatment of refractory B cell malignancies, but experience for solid tumors has proven challenging. We speculate that this is at least in part due to the poor quality of the patient's own T cells and therefore propose using CAR-modified cytokine-induced killer (CIK) cells as effector cells. CIK cells are a heterogeneous population of polyclonal T cells that acquire phenotypic and cytotoxic properties of natural killer (NK) cells through the cultivation process, becoming so-called T-NK cells. CIK cells can be genetically modified to express CARs. They are minimally alloreactive and can therefore be acquired from haploidentical first-degree relatives. Here, we explored the potential of ERBB2-CAR-modified random-donor CIK cells as a treatment for RMS in xenotolerant mice bearing disseminated high-risk RMS tumors. In otherwise untreated mice, RMS tumors engrafted 13-35 days after intravenous tumor cell injection, as shown by

Identifiants

pubmed: 33193388
doi: 10.3389/fimmu.2020.581468
pmc: PMC7641627
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0
Receptors, Chimeric Antigen 0
ERBB2 protein, human EC 2.7.10.1
Receptor, ErbB-2 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

581468

Informations de copyright

Copyright © 2020 Merker, Wagner, Kreyenberg, Heim, Moser, Wels, Bonig, Ivics, Ullrich, Klingebiel, Bader and Rettinger.

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Auteurs

Michael Merker (M)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.

Juliane Wagner (J)

Division of Medical Biotechnology, Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany.

Hermann Kreyenberg (H)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Catrin Heim (C)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Laura M Moser (LM)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Winfried S Wels (WS)

German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.

Halvard Bonig (H)

Department of Cellular Therapeutics/Cell Processing (Good Manufacturing Practice, GMP), Institute for Transfusion Medicine and Immunotherapy, Goethe University, Frankfurt, Germany.
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, United States.

Zoltán Ivics (Z)

Division of Medical Biotechnology, Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany.

Evelyn Ullrich (E)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Experimental Immunology, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.

Thomas Klingebiel (T)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.

Peter Bader (P)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.

Eva Rettinger (E)

Division for Stem Cell Transplantation, Immunology, and Intensive Care Medicine, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.

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Classifications MeSH