IL‐18R‐dependent and independent pathways account for IL‐18‐enhanced antitumor ability of CAR‐T cells

Huang, Yong; Li, Dan; Zhang, Peng-Fei; Liu, Mei; Liang, Xiao; Yang, Xiao; Jiang, Lin; Zhang, Lifeng; Zhou, Weilin; Su, Jinhua; Gong, Youling; Gou, Hongfeng; Wei, Yuquan; Wang, Wei

doi:10.1096/fj.201901809r

Cited by 20 publications

(11 citation statements)

References 49 publications

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“…In detail, they demonstrated that IL-18-secreting CAR-Ts can meaningfully prolong long-term survival in preclinical mouse models of hematologic and solid tumor neoplasms ( 162 ). Additionally, Huang and co-workers investigated the impacts of exogenous IL-18 on CAR-T tumoricidal activity and reported that IL-18 enhances the tumoricidal activity of HER2-redirected CAR-Ts in immunodeficient mice ( 165 ). These researchers also indicated that IL-18 demonstrates beneficial characteristics in improving ACT responses based on the finding that IL-18 enhanced the tumor-targeting capacity of OVA-specific T lymphocytes ( 165 ).…”

Section: Strategies For Amplifying Antitumor Responses Though the Ind...mentioning

confidence: 99%

Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Kozani

Najafabadi

et al. 2022

Front. Immunol.

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Chimeric antigen receptor T-cells (CAR-Ts) are known as revolutionary living drugs that have turned the tables of conventional cancer treatments in certain hematologic malignancies such as B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) by achieving US Food and Drug Administration (FDA) approval based on their successful clinical outcomes. However, this type of therapy has not seen the light of victory in the fight against solid tumors because of various restricting caveats including heterogeneous tumor antigen expression and the immunosuppressive tumor microenvironments (TME) that negatively affect the tumor-site accessibility, infiltration, stimulation, activation, and persistence of CAR-Ts. In this review, we explore strategic twists including boosting vaccines and designing implementations that can support CAR-T expansion, proliferation, and tumoricidal capacity. We also step further by underscoring novel strategies for triggering endogenous antitumor responses and overcoming the limitation of poor CAR-T tumor-tissue infiltration and the lack of definitive tumor-specific antigens. Ultimately, we highlight how these approaches can address the mentioned arduous hurdles.

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Section: Strategies For Amplifying Antitumor Responses Though the Ind...mentioning

confidence: 99%

Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Kozani

Najafabadi

et al. 2022

Front. Immunol.

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show abstract

“…Since, Yong Huang et al. ( 14 ) also found that exogenous IL-18 could improve the anti-tumor function of HER2-specific CAR-T cells in vitro and in vivo , not only in immunodeficient mice, but also in immunotolerant mice. In addition, Markus Chmielewski et al.…”

Section: Correlation Study Of Gene-edited Interleukin Car-t Cells In the Treatment Of Malignant Tumorsmentioning

confidence: 99%

Gene-Edited Interleukin CAR-T Cells Therapy in the Treatment of Malignancies: Present and Future

et al. 2021

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In recent years, chimeric antigen receptor T cells (CAR-T cells) have been faced with the problems of weak proliferation and poor persistence in the treatment of some malignancies. Researchers have been trying to perfect the function of CAR-T by genetically modifying its structure. In addition to the participation of T cell receptor (TCR) and costimulatory signals, immune cytokines also exert a decisive role in the activation and proliferation of T cells. Therefore, genetic engineering strategies were used to generate cytokines to enhance tumor killing function of CAR-T cells. When CAR-T cells are in contact with target tumor tissue, the proliferation ability and persistence of T cells can be improved by structurally or inductively releasing immunoregulatory molecules to the tumor region. There are a large number of CAR-T cells studies on gene-edited cytokines, and the most common cytokines involved are interleukins (IL-7, IL-12, IL-15, IL-18, IL-21, IL-23). Methods for the construction of gene-edited interleukin CAR-T cells include co-expression of single interleukin, two interleukin, interleukin combined with other cytokines, interleukin receptors, interleukin subunits, and fusion inverted cytokine receptors (ICR). Preclinical and clinical trials have yielded positive results, and many more are under way. By reading a large number of literatures, we summarized the functional characteristics of some members of the interleukin family related to tumor immunotherapy, and described the research status of gene-edited interleukin CAR-T cells in the treatment of malignant tumors. The objective is to explore the optimized strategy of gene edited interleukin-CAR-T cell function.

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“…IL-18, a member of the IL-1 superfamily, has been associated with human hemophagocytic lymphohistiocytosis (HLH) and systemic onset juvenile inflammatory arthritis 27 . IL-18, in cooperation with IL-12 or IL-15, stimulates T cells and NK cells, and induces IFN-γ secretion, thus promoting Th1 type inflammation 28 .…”

Section: Il-1mentioning

confidence: 99%

“…A recent study by the European Society for Blood and Marrow Transplantation (EBMT) has reported a 3%-4% incidence of sHLH/MAS after CAR T cell therapy 35 . However, IL-18 has been demonstrated to enhance the anti-tumor capacity of CAR T cells via an IL-18R independent route but not to increase the risk of CRS associated with CAR T cell therapy 28 .…”

Section: Il-1mentioning

confidence: 99%

Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome

Guo¹,

Qian²,

Cui³

2021

Cancer Biol. Med.

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Cytokine release syndrome (CRS) is a major obstacle to the widespread clinical application of chimeric antigen receptor (CAR) T cell therapies. CRS can also be induced by infections (such as SARS-CoV-2), drugs (such as therapeutic antibodies), and some autoimmune diseases. Myeloid-derived macrophages play key roles in the pathogenesis of CRS, and participate in the production and release of the core CRS cytokines, including interleukin (IL)-1, IL-6, and interferon-γ. In this review, we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.

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IL‐18R‐dependent and independent pathways account for IL‐18‐enhanced antitumor ability of CAR‐T cells

Cited by 20 publications

References 49 publications

Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Gene-Edited Interleukin CAR-T Cells Therapy in the Treatment of Malignancies: Present and Future

Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome

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