Advances in Universal CAR-T Cell Therapy

Lin, Haolong; Cheng, Jiali; Mu, Wei; Zhou, Jianfeng; Zhu, Li

doi:10.3389/fimmu.2021.744823

Cited by 114 publications

(122 citation statements)

References 84 publications

(100 reference statements)

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“…The unique characteristics of these agents not only grant them irreplaceable advantages but also give them inevitable limitations. For instance, anti-BCMA CAR-T-cell therapy with better performance requires more complex preparation conditions and more expensive treatment costs, which are difficult for ordinary families to afford ( 130 ). For BsAbs, because of the relatively short half-life period ( 131 ), they need to extend the infusion time or improve the medication frequency to maintain its efficacy ( 132 ), which also increases the costs of treatment.…”

Section: Discussionmentioning

confidence: 99%

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

Guo

Zhang

et al. 2022

Front. Immunol.

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With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63rd annual meeting of the American Society of Hematology updated some information about the application of BCMA in MM. This review summarizes part of the related points presented at this conference.

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Section: Discussionmentioning

confidence: 99%

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

Guo

Zhang

et al. 2022

Front. Immunol.

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“…TMs are short-lived molecules with an epitope and a specific tumor antigen-binding domain. As UniCAR systems are controlled by TM, their efficiency and associated toxicities can be managed by titration of TM ( Cartellieri et al, 2015 ; Cartellieri et al, 2016 ; Albert et al, 2017 ; Feldmann et al, 2017 ; Bachmann et al, 2018 ; Loureiro et al, 2018 ; Bachmann, 2019 ; Jureczek et al, 2019 ; Arndt et al, 2020 ; Lin et al, 2021 ). CAAR T cell therapy is directed toward autoimmunity, more specifically toward B cell-mediated autoimmune disorders.…”

Section: Current Protocols and Future Perspectives In T Cell Expansionmentioning

confidence: 99%

Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions

Sudarsanam

Buhmann

Henschler

2022

Front. Bioeng. Biotechnol.

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Ex vivo expansion of T lymphocytes is a central process in the generation of cellular therapies targeted at tumors and other disease-relevant structures, which currently cannot be reached by established pharmaceuticals. The influence of culture conditions on T cell functions is, however, incompletely understood. In clinical applications of ex vivo expanded T cells, so far, a relatively classical standard cell culture methodology has been established. The expanded cells have been characterized in both preclinical models and clinical studies mainly using a therapeutic endpoint, for example antitumor response and cytotoxic function against cellular targets, whereas the influence of manipulations of T cells ex vivo including transduction and culture expansion has been studied to a much lesser detail, or in many contexts remains unknown. This includes the circulation behavior of expanded T cells after intravenous application, their intracellular metabolism and signal transduction, and their cytoskeletal (re)organization or their adhesion, migration, and subsequent intra-tissue differentiation. This review aims to provide an overview of established T cell expansion methodologies and address unanswered questions relating in vivo interaction of ex vivo expanded T cells for cellular therapy.

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“…TALEN and CRISPR/Cas9 are the two most commonly used gene-editing methods. The main targets of U-CAR-T cell clinical trials include CD19, BCMA, CD7, CD22, CD123, CS1, and mesothelin [66] . Allogeneic CD19 CAR-T cell by silencing T-cell receptor α constant (TRAC) was first reported in 2012 [67] .…”

Section: Gene and Protein In Diseasementioning

confidence: 99%

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

Chen¹,

Li²,

Zhang³

et al. 2022

GPD

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Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

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Advances in Universal CAR-T Cell Therapy

Cited by 114 publications

References 84 publications

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting

Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

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