Dataset Information

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

ABSTRACT: 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.

SUBMITTER: Jin L

PROVIDER: S-EPMC6728370 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

Jin Linchun L Tao Haipeng H Karachi Aida A Long Yu Y Hou Alicia Y AY Na Meng M Dyson Kyle A KA Grippin Adam J AJ Deleyrolle Loic P LP Zhang Wang W Rajon Didier A DA Wang Qiong J QJ Yang James C JC Kresak Jesse L JL Sayour Elias J EJ Rahman Maryam M Bova Frank J FJ Lin Zhiguo Z Mitchell Duane A DA Huang Jianping J

Nature communications 20190905 1

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 act ...[more]

PMID: 31488817

Dataset Information

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

Publications

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

The antitumor capacity of mesothelin-CAR-T cells in targeting solid tumors in mice.
| S-EPMC7943972 | biostudies-literature

B7-H3-Targeted CAR-T Cells Exhibit Potent Antitumor Effects on Hematologic and Solid Tumors.
| S-EPMC7178328 | biostudies-literature

Critical factors in chimeric antigen receptor-modified T-cell (CAR-T) therapy for solid tumors.
| S-EPMC6309774 | biostudies-literature

Making CAR T Cells a Solid Option for Solid Tumors.
| S-EPMC6235951 | biostudies-literature

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.
| S-EPMC6572851 | biostudies-literature

Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils.
| S-EPMC10715261 | biostudies-literature

IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors.
| S-EPMC7647667 | biostudies-literature

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors.
| S-EPMC8722110 | biostudies-literature

Differences in Sulfotyrosine Binding amongst CXCR1 and CXCR2 Chemokine Ligands.
| S-EPMC5618543 | biostudies-literature

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion.
| S-EPMC2696769 | biostudies-literature