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Curated Papers > Recent high-impact research on "CAR-T therapy" (IF≥30, last 5 years)

CAR T therapy beyond cancer: the evolution of a living drug. ​

Literature Information ​

DOI10.1038/s41586-023-06243-w
PMID37495877
JournalNature
Impact Factor48.5
JCR QuartileQ1
Publication Year2023
Times Cited165
KeywordsCAR T therapy, oncology, autoimmunity, chronic infections, cardiac fibrosis
Literature TypeJournal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN0028-0836
Pages707-715
Issue619(7971)
AuthorsDaniel J Baker, Zoltan Arany, Joseph A Baur, Jonathan A Epstein, Carl H June

TL;DR ​

This review explores the expanding potential of chimaeric antigen receptor (CAR) T therapy beyond oncology, highlighting its promising applications in treating autoimmune diseases, chronic infections, and other non-cancerous conditions, while addressing current challenges in specificity and safety. The findings emphasize the need for innovative technologies to enhance CAR T therapy's efficacy across various medical contexts.

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CAR T therapy · oncology · autoimmunity · chronic infections · cardiac fibrosis

Abstract ​

Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.

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Primary Questions Addressed ​

  1. What are the specific mechanisms by which CAR T therapy can be adapted to treat autoimmune diseases?
  2. How do the safety and efficacy profiles of CAR T therapy in chronic infections compare to its use in oncology?
  3. What technological advancements are currently being explored to enhance CAR T therapy for non-cancerous applications?
  4. In what ways could CAR T therapy be integrated into existing treatment protocols for cardiac fibrosis?
  5. What challenges must be overcome to ensure the specificity of CAR T therapy in treating senescence-associated diseases?

Key Findings ​

Research Background and Objectives ​

Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in treating patients with untreatable hematologic cancers, leading to a growing interest in its application across various medical fields. This review aims to explore the rationale for CAR T therapy, the challenges encountered in oncology, preliminary findings in non-cancerous diseases, and emerging technologies that could expand its use beyond cancer.

Main Methods/Materials/Experimental Design ​

The review synthesizes findings from clinical and preclinical studies, focusing on the application of CAR T therapy in both oncology and non-oncology contexts. The following key components are involved in the exploration of CAR T therapy:

Mermaid diagram

Key Results and Findings ​

  • Oncology Applications: CAR T therapy has successfully treated various hematologic malignancies, leading to complete remissions in some patients.
  • Non-Oncology Applications: Preliminary studies suggest potential benefits of CAR T therapy in treating:
    • Chronic infections (e.g., HIV)
    • Autoimmune diseases (e.g., lupus)
    • Cardiac fibrosis
    • Age-related diseases
  • Emerging Technologies: New platforms and technologies, such as next-generation CAR designs and enhanced targeting mechanisms, are being developed to improve the efficacy and safety of CAR T therapies.

Main Conclusions/Significance/Innovativeness ​

The findings suggest that CAR T therapy holds promise not only in oncology but also in addressing a variety of non-cancerous diseases. The innovative application of CAR T therapy could lead to breakthroughs in treating chronic and autoimmune conditions, thus expanding the therapeutic landscape. However, challenges related to specificity and safety must be addressed to ensure the safe application of CAR T therapies in broader contexts.

Research Limitations and Future Directions ​

  • Limitations:

    • The review primarily focuses on preliminary reports, which may not provide comprehensive insights into the long-term efficacy and safety of CAR T therapy in non-cancerous diseases.
    • The challenges related to specificity and safety remain inadequately addressed in current studies.

  • Future Directions:

    • Continued research is needed to refine CAR T therapy for non-cancer applications, particularly in improving targeting mechanisms to minimize off-target effects.
    • Clinical trials are essential to evaluate the long-term outcomes and safety profiles of CAR T therapy in various non-oncological conditions.
    • Exploration of combination therapies with CAR T cells to enhance therapeutic effects in chronic and autoimmune diseases is recommended.

References ​

  1. 'Off-the-shelf' allogeneic CAR T cells: development and challenges. - S Depil;P Duchateau;S A Grupp;G Mufti;L Poirot - Nature reviews. Drug discovery (2020)
  2. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. - Katharina Reinhard;Benjamin Rengstl;Petra Oehm;Kristina Michel;Arne Billmeier;Nina Hayduk;Oliver Klein;Kathrin Kuna;Yasmina Ouchan;Stefan Wöll;Elmar Christ;David Weber;Martin Suchan;Thomas Bukur;Matthias Birtel;Veronika Jahndel;Karolina Mroz;Kathleen Hobohm;Lena Kranz;Mustafa Diken;Klaus Kühlcke;Özlem Türeci;Ugur Sahin - Science (New York, N.Y.) (2020)
  3. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. - Christian L Flugel;Robbie G Majzner;Giedre Krenciute;Gianpietro Dotti;Stanley R Riddell;Dimitrios L Wagner;Mohamed Abou-El-Enein - Nature reviews. Clinical oncology (2023)
  4. Targeting of human immunodeficiency virus-infected cells by CD8+ T lymphocytes armed with universal T-cell receptors. - M R Roberts;L Qin;D Zhang;D H Smith;A C Tran;T J Dull;J E Groopman;D J Capon;R A Byrn;M H Finer - Blood (1994)
  5. Thermogenic T cells: a cell therapy for obesity? - Ulf H Beier;Daniel J Baker;Joseph A Baur - American journal of physiology. Cell physiology (2022)
  6. Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer. - Julia Tchou;Yangbing Zhao;Bruce L Levine;Paul J Zhang;Megan M Davis;Jan Joseph Melenhorst;Irina Kulikovskaya;Andrea L Brennan;Xiaojun Liu;Simon F Lacey;Avery D Posey;Austin D Williams;Alycia So;Jose R Conejo-Garcia;Gabriela Plesa;Regina M Young;Shannon McGettigan;Jean Campbell;Robert H Pierce;Jennifer M Matro;Angela M DeMichele;Amy S Clark;Laurence J Cooper;Lynn M Schuchter;Robert H Vonderheide;Carl H June - Cancer immunology research (2017)
  7. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. - Reuben Benjamin;Charlotte Graham;Deborah Yallop;Agnieszka Jozwik;Oana C Mirci-Danicar;Giovanna Lucchini;Danielle Pinner;Nitin Jain;Hagop Kantarjian;Nicolas Boissel;Marcela V Maus;Matthew J Frigault;André Baruchel;Mohamad Mohty;Athos Gianella-Borradori;Florence Binlich;Svetlana Balandraud;Fabien Vitry;Elisabeth Thomas;Anne Philippe;Sylvain Fouliard;Sandra Dupouy;Ibtissam Marchiq;Maria Almena-Carrasco;Nicolas Ferry;Sylvain Arnould;Cyril Konto;Paul Veys;Waseem Qasim; - Lancet (London, England) (2020)
  8. CAR T therapy extends its reach to autoimmune diseases. - Daniel J Baker;Carl H June - Cell (2022)
  9. Engineering Antibodies Targeting p16 MHC-Peptide Complexes. - Nicholas J Rettko;Judith Campisi;James A Wells - ACS chemical biology (2022)
  10. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. - Masayoshi Suda;Ippei Shimizu;Goro Katsuumi;Yohko Yoshida;Yuka Hayashi;Ryutaro Ikegami;Naomi Matsumoto;Yutaka Yoshida;Ryuta Mikawa;Akihiro Katayama;Jun Wada;Masahide Seki;Yutaka Suzuki;Atsushi Iwama;Hironori Nakagami;Ayako Nagasawa;Ryuichi Morishita;Masataka Sugimoto;Shujiro Okuda;Masanori Tsuchida;Kazuyuki Ozaki;Mayumi Nakanishi-Matsui;Tohru Minamino - Nature aging (2021)

Literatures Citing This Work ​

  1. LIGHTing CAR T in the tumor microenvironment. - Yong Liang;Yang-Xin Fu - Molecular therapy : the journal of the American Society of Gene Therapy (2023)
  2. Recombinant oncolytic adenovirus armed with CCL5, IL-12, and IFN-γ promotes CAR-T infiltration and proliferation in vivo to eradicate local and distal tumors. - Lin Fang;Sen Yuan;Meng Wang;Chen Zhang;Xueyan Wang;Hailong Li;Jie Yang;Wanjing Li;Nan Sun;Qi Zhang;Yuxin Zhang;Dafei Chai;Huizhong Li;Junnian Zheng;Gang Wang - Cell death discovery (2023)
  3. CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo. - Vita Golubovskaya;John Sienkiewicz;Jinying Sun;Shiming Zhang;Yanwei Huang;Hua Zhou;Hizkia Harto;Shirley Xu;Robert Berahovich;Lijun Wu - International journal of molecular sciences (2023)
  4. A Genetically Encoded Dark-to-Bright Biosensor for Visualisation of Granzyme-Mediated Cytotoxicity. - Christopher Bednar;Sabrina Kübel;Arne Cordsmeier;Brigitte Scholz;Hanna Menschikowski;Armin Ensser - International journal of molecular sciences (2023)
  5. Advances in CAR-Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies. - Zhaozhao Chen;Yu Hu;Heng Mei - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  6. CAR-T Cell Therapy: From the Shop to Cancer Therapy. - Ashanti Concepción Uscanga-Palomeque;Ana Karina Chávez-Escamilla;Cynthia Aracely Alvizo-Báez;Santiago Saavedra-Alonso;Luis Daniel Terrazas-Armendáriz;Reyes S Tamez-Guerra;Cristina Rodríguez-Padilla;Juan Manuel Alcocer-González - International journal of molecular sciences (2023)
  7. Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases. - Xia Lyu;Latika Gupta;Eleni Tholouli;Hector Chinoy - Rheumatology (Oxford, England) (2024)
  8. Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape. - Androulla N Miliotou;Sofia K Georgiou-Siafis;Charikleia Ntenti;Ioannis S Pappas;Lefkothea C Papadopoulou - Current issues in molecular biology (2023)
  9. Rationally designed approaches to augment CAR-T therapy for solid tumor treatment. - Chaojie Zhu;Qing Wu;Tao Sheng;Jiaqi Shi;Xinyuan Shen;Jicheng Yu;Yang Du;Jie Sun;Tingxizi Liang;Kaixin He;Yuan Ding;Hongjun Li;Zhen Gu;Weilin Wang - Bioactive materials (2024)
  10. The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases. - Zhuoqun Liu;Yuchen Xiao;Jianjun Lyu;Duohui Jing;Liu Liu;Yanbin Fu;Wenxin Niu;Lingjing Jin;Chao Zhang - Protein & cell (2024)

... (155 more literatures)

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