Shifting the Evolving CAR T Cell Platform into Higher Gear

Holohan, Daniel R.; Lee, James C.; Bluestone, Jeffrey A.

doi:10.1016/j.ccell.2015.09.014

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…Some recent reports have revealed that second-generation CARs constitutively expressing ligands for CD28 or 4/1BB (CD80 or 4/1BBL, respectively) enhance T cell activity in vivo [ 104 ]. Stephan and colleagues suggested that the 4/1BB-4/1BBL signaling pathway may more effectively enhance CAR modified-T cell activation and cytotoxicity, potentially in a bidirectional manner with direct signaling within the T cells themselves and indirect triggering of other immune cells expressing the 4/1BB domain in the TME (Fig.…”

Section: Approaches To Improve the Car-t Cell Efficacymentioning

confidence: 99%

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Zhang

2018

Mol Cancer

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The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication.

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Section: Approaches To Improve the Car-t Cell Efficacymentioning

confidence: 99%

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Zhang

2018

Mol Cancer

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“…Although CAR-T cells have presented great promise for clinical applications, there are two main problems that can arise: CRS and in the case of anti-CD19 CAR-T cells, B-cell aplasia and subsequent immunodepression [ 23 , 32 - 34 ]. One of the solutions used in this regard is the use of switch molecules, like rimiducid, to control CAR-T cells activity [ 35 - 37 ].…”

Section: Introductionmentioning

confidence: 99%

Genetically enhanced T lymphocytes and the intensive care unit

Tat

Constantinescu

et al. 2018

Oncotarget

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Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment.

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“…Another second-generation CAR construct incorporating CD28 signaling domain proved efficiency for 21 chemotherapy-resistant B precursor ALL patients (70% complete remission rate) without encountering prolonged B-cell aplasia after. In addition, the other side effects such as CRS were reversible ( 144 ). CAR T-cell-based therapy represents external stimuli that might be significant on the immune system.…”

Section: Second-generation Car Constructs For Hematological Malignancmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

et al. 2018

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Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

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Shifting the Evolving CAR T Cell Platform into Higher Gear

Cited by 7 publications

References 8 publications

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Genetically enhanced T lymphocytes and the intensive care unit

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

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