30
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      CAR-T cell therapy: current limitations and potential strategies

      review-article
      1 , 2 ,
      Blood Cancer Journal
      Nature Publishing Group UK
      Immunotherapy, Cancer immunotherapy

      Read this article at

      Bookmark
          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

          Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.

          Related collections

          Most cited references106

          • Record: found
          • Abstract: found
          • Article: not found

          Microenvironmental regulation of tumor progression and metastasis.

          Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

            In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

              In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
                Bookmark

                Author and article information

                Contributors
                sterner.rosalie@mayo.edu
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                6 April 2021
                6 April 2021
                April 2021
                : 11
                : 4
                : 69
                Affiliations
                [1 ]GRID grid.471391.9, Medical Scientist Training Program, , University of Wisconsin-Madison, School of Medicine and Public Health, ; Madison, WI USA
                [2 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Department of Surgery, , Mayo Clinic, ; Rochester, MN USA
                Author information
                http://orcid.org/0000-0001-8195-4970
                http://orcid.org/0000-0002-9323-3625
                Article
                459
                10.1038/s41408-021-00459-7
                8024391
                33824268
                b5d9c351-bae5-4ee1-bc24-24925ca4142c
                © The Author(s) 2021

                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
                : 27 November 2020
                : 24 February 2021
                : 8 March 2021
                Funding
                Funded by: Supported by University of Wisconsin-Madison Medical Scientist Training Program T32GM008692
                Funded by: Regenerative Medicine Minnesota RMM 012819 EPC 003
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                immunotherapy,cancer immunotherapy
                Oncology & Radiotherapy
                immunotherapy, cancer immunotherapy

                Comments

                Comment on this article