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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [scRNA-Seq]

ABSTRACT: Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [scRNA-Seq]

PROVIDER: PRJNA664024 | ENA |

REPOSITORIES: ENA

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade

Project description:Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [RNA-Seq]

Project description:CAR-T cell therapy is effective in hematologic malignancies but not in solid tumors. In breast and lung cancer patients, CAR-T cells targeting ROR1 infiltrated tumors poorly and became dysfunctional. To test strategies for enhancing efficacy, we induced ROR1+ lung tumors in KrasLSL-G12D/+;p53fl/f mice. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently controlled tumor growth but infiltrated tumors poorly and lost function, as observed in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activated tumor macrophages to express T cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improved CAR-T mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [scRNA-Seq]

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [RNA-Seq]

Project description:Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade [RNA-Seq]

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to solid tumors and improves anti-tumor efficacy when combined with checkpoint blockade

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-09-18 | GSE158111 | GEO

Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade.

Project description:Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the KrasLSL-G12D/+;p53f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

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NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [RNA-Seq]

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