CAR T‐cell therapy of solid tumors

Yong, Carmen S.; Dardalhon, Valérie; Devaud, Christel; Taylor, Naomi; Darcy, Phillip K.; Kershaw, Michael H.

doi:10.1038/icb.2016.128

Cited by 165 publications

(156 citation statements)

References 65 publications

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“…Consequently, in principle, CAR therapy is restricted to targeting cell surface molecules uniquely expressed by tumor cells or those that are only expressed by dispensable normal tissues (Kakarla and Gottschalk, 2014). Due to a lack of such targets (Klebanoff et al, 2016), and perhaps a number of other factors that are incompletely elucidated (Yong et al, 2017), CAR therapy has shown extremely limited efficacy against solid tumors.…”

Section: Principles Of Immunotherapy To Treat Human Cancermentioning

confidence: 99%

Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

2017

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Summary Cancer immunotherapy is an increasingly successful strategy for the treatment of patients who have advanced or conventional therapy-resistant cancers. T cells are key mediators of tumor destruction and their specificity for tumor-expressed antigens is of paramount importance, but other T cell-intrinsic qualities such as durability, longevity and functionality also play important roles in determining the efficacy of immunotherapy. The cellular energetic pathways that are utilized by T cells play a key role in regulating each of these qualities. Metabolic activity, which both regulates and is regulated by cellular signaling pathways and epigenetics, also profoundly influences the trajectories of T cell differentiation and fate. In this review, we discuss how cell metabolism influences T cell anti-tumor activity, the metabolic qualities of highly-functional T cells and strategies to modulate metabolism for improving the immune response to tumors.

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Section: Principles Of Immunotherapy To Treat Human Cancermentioning

confidence: 99%

Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

2017

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“…As there are several excellent reviews summarizing the recent information about clinical trials in the field of CAR-T 20–23 , we will omit the detailed description of clinical trial data in this review, to avoid duplication.…”

Section: Car Design and Therapeutic Efficacymentioning

confidence: 99%

The biological basis and clinical symptoms of CAR-T therapy-associated toxicites

et al. 2018

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Currently, immunotherapy is attracting a lot of attention and may potentially become a leading approach in the treatment of cancer. One emerging therapeutic, the chimeric-antigen receptor T-cell adoptive immunotherapy (CAR-T) is showing remarkable efficacy in the treatment of several B-cell malignancies. The popularity of CAR-T has been founded on two CAR T-cell products recently approved by FDA (during 2017) in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia and B-cell lymphoma. However, their toxicities observed in clinical trials were extremely significant and in some cases even fatal with no approved algorithms for toxicity prediction being available to date. A deeper understanding of the biological basis of such complications is the key to prompt and comprehensive clinical management. Here we review the wide spectrum of effects associated with CAR T cell therapy with a major focus on the pathogenesis of cytokine release syndrome and neurotoxicity as the most common, potentially life-threatening effects of this treatment. We discuss the basis of clinical management and the existing models that predict the severity of toxicity, as well as the key factors that modulate this event. Finally, we will summarize the literature detailing universal allogenic CAR T-cells and their toxicity profile.

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“…Other obstacles to optimal CAR-T cell function are related to tumor microenvironment and include lack of chemotactic homing signals, lack of costimulatory molecules for T-cells, abnormal tumor vasculature and immunesuppressive cells. [111] Approaches to overcome obstacles to anti-GD2 CAR T-cell activity against neuroblastoma include incorporation of costimulatory molecules such as 4–1BB[112] and combination with PD-1 blockade. [113] The expansion of T-cell subpopulations such as CD4+ cells or central memory cells transfected with CAR is also being investigated.…”

Section: Preclinical Approachesmentioning

confidence: 99%

Anti-GD2 immunotherapy for neuroblastoma

Sait

Modak

2017

Expert Review of Anticancer Therapy

138

133

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Introduction: Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development. Expert commentary: Anti-GD2 monoclonal antibodies are associated with improved survival in patients in their first remission and are increasingly being used for chemorefractory and relapsed neuroblastoma. As protein engineering technology has become more accessible, newer antibody constructs are being tested. GD2 is also being targeted by natural killer cells and T-cells. Active immunity can be elicited by anti-GD2 vaccines. The rational combination of currently available and soon-to-emerge immunotherapeutic approaches, and their integration into conventional multimodality therapies will require further investigation to optimize their use for HR-NB.

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CAR T‐cell therapy of solid tumors

Cited by 165 publications

References 65 publications

Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

The biological basis and clinical symptoms of CAR-T therapy-associated toxicites

Anti-GD2 immunotherapy for neuroblastoma

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