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      CAR-T cells: the long and winding road to solid tumors

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the “next generation” of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host’s defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

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          Most cited references68

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          The blockade of immune checkpoints in cancer immunotherapy.

          Drew M Pardoll (2012)
          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
          Article 0 comments Cited 5129 times – based on 0 reviews     Review now
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            CTLA-4 and PD-1 Pathways

            Elizabeth I Buchbinder, Anupam Desai (2016)
            Supplemental Digital Content is available in the text.
            Article 0 comments Cited 807 times – based on 0 reviews     Review now
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              Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

              Christine E. Brown, Darya Alizadeh, Renate Starr … (2016)
              A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).
              Article 0 comments Cited 724 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Maurizio Alimandi: 39-06-33775257 , maurizio.alimandi@uniroma1.it
                Journal
                Journal ID (nlm-ta): Cell Death Dis
                Journal ID (iso-abbrev): Cell Death Dis
                Title: Cell Death & Disease
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2041-4889
                Publication date (Electronic): 15 February 2018
                Publication date PMC-release: 15 February 2018
                Publication date Collection: March 2018
                Volume: 9
                Issue: 3
                Electronic Location Identifier: 282
                Affiliations
                [1 ]GRID grid.7841.a, Department of Clinical and Molecular Medicine, , Sapienza University of Rome, ; Rome, Italy
                [2 ]GRID grid.7841.a, Department of Experimental Medicine, , Sapienza University of Rome, ; Rome, Italy
                [3 ]ISNI 0000000121622106, GRID grid.8509.4, Department of Science, , University Roma Tre, ; Rome, Italy
                Article
                Publisher ID: 278
                DOI: 10.1038/s41419-018-0278-6
                PMC ID: 5833816
                PubMed ID: 29449531
                SO-VID: 6f63c49d-c940-4f64-a005-774782b0a60e
                Copyright © © The Author(s) 2018
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 3 October 2017
                Date revision received : 18 December 2017
                Date accepted : 21 December 2017
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Cell biology
                Data availability:
                ScienceOpen disciplines: Cell biology

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