2017
DOI: 10.3389/fimmu.2017.00267
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Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don’t Forget the Fuel

Abstract: T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors th… Show more

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Cited by 67 publications
(64 citation statements)
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“…Chimeric antigen receptor (CAR) is a genetically engineered T‐cell receptor where the intracellular signalling domain is activated by extracellular single‐chain variable fragments upon direct binding to a specific protein expressed on the surface of tumour cells. Therefore, CAR‐T cells can exert cytotoxicity against tumour cells expressing the target surface molecules without MHC‐I‐restricted antigen presentation . The CAR‐T‐cell transfer therapy has been successful for B lymphoma, but its applicability to solid tumours is still under investigation .…”
Section: Tam Targeting For Adoptive Ctl Transfer Therapymentioning
confidence: 99%
“…Chimeric antigen receptor (CAR) is a genetically engineered T‐cell receptor where the intracellular signalling domain is activated by extracellular single‐chain variable fragments upon direct binding to a specific protein expressed on the surface of tumour cells. Therefore, CAR‐T cells can exert cytotoxicity against tumour cells expressing the target surface molecules without MHC‐I‐restricted antigen presentation . The CAR‐T‐cell transfer therapy has been successful for B lymphoma, but its applicability to solid tumours is still under investigation .…”
Section: Tam Targeting For Adoptive Ctl Transfer Therapymentioning
confidence: 99%
“…After infusion into a patient, the T cells must traffic to the tumour site, infiltrate the tumour stroma and engage the specific TAA on malignant cells. Then, they must rapidly expand to high numbers in response to an antigen and mount the attack on cancer cells within a harsh tumour microenvironment that features multiple physical barriers 97-99 , a biochemical and metabolic milieu that is unfavourable to T-cell effector function [100][101][102] , and immunosuppression signals from an arsenal of inhibitory molecules displayed or secreted by cancer cells and supporting stromal cells alike 103-105 (Fig. 6).…”
Section: Improving Efficacy and Overcoming Immune Suppressionmentioning
confidence: 99%
“…Consequently, the metabolic profile of T cells is intimately linked to the regulation of T-cell function and differentiation stage. The aberrant metabolic milieu in tumour microenvironments, as a result of the high metabolic activity of tumour cells and dysfunctional tumour vasculature, is both hypoxic and acidic, depleted of nutrients such as glucose and glutamine, and lacks key amino acids such as arginine and tryptophan due to the upregulation of the inhibitory enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and arginase by the tumour stroma 100 . This unfavourable environment inhibits T-cell effector functions and promotes a defective T-cell state.…”
Section: Nature Biomedical Engineeringmentioning
confidence: 99%
“…However, current T cell therapies had a limited clinical response in solid tumors [83]. Therefore, there are emerging challenges in the field of T cell-based immunotherapy for solid tumors: (1) how can we expand less-differentiated engineered T cell subsets in vitro; and (2) [84].…”
Section: Integrating Mirnas Into the Design Of Future Immunotherapeutmentioning
confidence: 99%