Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives

Gauthier, Jordan; Yakoub-Agha, Ibrahim

doi:10.1016/j.retram.2017.08.003

Cited by 91 publications

(62 citation statements)

References 72 publications

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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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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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“…Studies have shown that tumors possessing these antigens are more likely to induce tolerance and are less responsive to ICB (further explained below) (22,23). In addition, they induce more autoreactivity when targeted by adoptive cell therapy (ACT) (31)(32)(33)(34)(35)(36).…”

Section: Tumor Immunosurveillance and Tumor Antigensmentioning

confidence: 99%

“…In depth investigation of the mechanism of action of TCRengineered TILs identified the need for MHC recognition as a major limitation due to the MHC-downregulating nature of some tumors. To circumvent that, co-transduction of a chimeric antigen receptor (CAR) was investigated (36). CARs are synthetic receptors that enhance T-cell antitumor effector function and produce superior anti-cancer activity as seen in successful outcomes of clinical trials treating patients with B cell hematologic malignancies (91).…”

Section: Adoptively Transferred Tumor Reactive T Cellsmentioning

confidence: 99%

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

et al. 2020

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“…CAR-T cells targeting CD19 are effective in the treatment of malignant hematological diseases in preclinical and clinical trials. 182,187,188 They were approved by the US food and drug administration for clinical treatments in 2017. This technology has shown its full potential in cancer therapy, it is now extended to therapies using Tregs.…”

Section: Tcr/car and Othersmentioning

confidence: 99%

Future prospects for CD8⁺ regulatory T cells in immune tolerance

Flippe

Bézie

Anegón

et al. 2019

Immunological Reviews

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CD8+ Tregs have been long described and significant progresses have been made about their phenotype, their functional mechanisms, and their suppressive ability compared to conventional CD4+ Tregs. They are now at the dawn of their clinical use. In this review, we will summarize their phenotypic characteristics, their mechanisms of action, the similarities, differences and synergies between CD8+ and CD4+ Tregs, and we will discuss the biology, development and induction of CD8+ Tregs, their manufacturing for clinical use, considering open questions/uncertainties and future technically accessible improvements notably through genetic modifications.

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Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives

Cited by 91 publications

References 72 publications

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

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

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Future prospects for CD8⁺ regulatory T cells in immune tolerance

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Chimeric antigen-receptor T-cell therapy for hematological malignancies and solid tumors: Clinical data to date, current limitations and perspectives

Cited by 91 publications

References 72 publications

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

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

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Future prospects for CD8+ regulatory T cells in immune tolerance

Contact Info

Product

Resources

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Future prospects for CD8⁺ regulatory T cells in immune tolerance