Nature communications, 2019-09, Vol.10 (1), p.4016-13, Article 4016
2019
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Details
- Autor(en) / Beteiligte
- Titel
- CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors
- Ist Teil von
- Nature communications, 2019-09, Vol.10 (1), p.4016-13, Article 4016
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors. Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which induce complete tumor regression and long-lasting immunologic memory in pre-clinical models of aggressive tumors such as glioblastoma, ovarian and pancreatic cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-11869-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_de9a908e5e6e46b0b45bc79a9225470e
- Format
- –
- Schlagworte
- Animals, Anticancer properties, Antigens, Antigens, Neoplasm - immunology, Antitumor activity, Brain Neoplasms - pathology, Cell Line, Tumor, Cell Proliferation, Cell survival, Chimeric antigen receptors, CXCR2 protein, Cytokines - metabolism, Disease Models, Animal, Female, Glioblastoma, Glioblastoma - drug therapy, Glioblastoma - immunology, Glioblastoma - pathology, Heterogeneity, Humans, Immunotherapy, Adoptive, Interleukin 8, Interleukin-8 - metabolism, Lymphocytes, Lymphocytes T, Mice, Inbred NOD, Microenvironments, Ovarian cancer, Pancreatic cancer, Receptors, Antigen, T-Cell - immunology, Receptors, Interleukin-8A - metabolism, Receptors, Interleukin-8B - metabolism, Solid tumors, T-Lymphocytes - immunology, Tumor Microenvironment - immunology, Tumors, Xenograft Model Antitumor Assays