MaltSci 麦伴科研

Appearance

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

Chimeric antigen receptor T cell therapy for autoimmune disease. ​

Literature Information ​

DOI10.1038/s41577-024-01035-3
PMID38831163
JournalNature reviews. Immunology
Impact Factor60.9
JCR QuartileQ1
Publication Year2024
Times Cited24
KeywordsChimeric Antigen Receptor T Cell Therapy, Autoimmune Disease, B Cells, Clinical Trials, Immune Modulation
Literature TypeJournal Article, Review
ISSN1474-1733
Pages830-845
Issue24(11)
AuthorsJames B Chung, Jennifer N Brudno, Dominic Borie, James N Kochenderfer

TL;DR ​

This research highlights the potential of CAR T cell therapy, originally successful for B cell malignancies, to treat autoimmune diseases by targeting specific B cell proteins like CD19. It discusses promising clinical trial results and emphasizes the need for careful consideration of target populations, CAR design, and safety to ensure effective and lasting immune modulation in autoimmune conditions.

Search for more papers on MaltSci.com ​

Chimeric Antigen Receptor T Cell Therapy · Autoimmune Disease · B Cells · Clinical Trials · Immune Modulation

Abstract ​

Infusion of T cells engineered to express chimeric antigen receptors (CARs) that target B cells has proven to be a successful treatment for B cell malignancies. This success inspired the development of CAR T cells to selectively deplete or modulate the aberrant immune responses that underlie autoimmune disease. Promising results are emerging from clinical trials of CAR T cells targeting the B cell protein CD19 in patients with B cell-driven autoimmune diseases. Further approaches are being designed to extend the application and improve safety of CAR T cell therapy in the setting of autoimmunity, including the use of chimeric autoantibody receptors to selectively deplete autoantigen-specific B cells and the use of regulatory T cells engineered to express antigen-specific CARs for targeted immune modulation. Here, we highlight important considerations, such as optimal target cell populations, CAR construct design, acceptable toxicities and potential for lasting immune reset, that will inform the eventual safe adoption of CAR T cell therapy for the treatment of autoimmune diseases.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What are the specific challenges in designing CAR T cell therapies for different types of autoimmune diseases?
  2. How do the mechanisms of CAR T cell therapy differ when targeting B cells in malignancies versus autoimmune diseases?
  3. What are the potential long-term effects of CAR T cell therapy on the immune system in patients with autoimmune disorders?
  4. How do regulatory T cells engineered with antigen-specific CARs enhance the safety and efficacy of treatment in autoimmune conditions?
  5. What are the current clinical trial outcomes for CAR T cell therapies targeting CD19 in patients with autoimmune diseases?

Key Findings ​

Research Background and Purpose ​

The advent of chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of B cell malignancies, demonstrating significant efficacy in targeting B cells. This success has prompted researchers to explore the potential of CAR T cells in addressing autoimmune diseases characterized by aberrant immune responses. The primary aim of this study is to investigate the application of CAR T cells in selectively depleting or modulating B cells involved in autoimmune disorders, with a focus on the promising outcomes observed in clinical trials targeting the B cell protein CD19.

Main Methods/Materials/Experimental Design ​

The research outlines various innovative approaches in CAR T cell therapy for autoimmune diseases, which can be structured as follows:

Mermaid diagram
  1. Targeting CD19: This involves engineering T cells to express CARs that specifically recognize CD19 on B cells, which has shown promise in clinical settings.
  2. Chimeric Autoantibody Receptors: These are designed to selectively target and deplete B cells that produce autoantibodies, thus addressing the root cause of certain autoimmune conditions.
  3. Regulatory T Cells: Engineering T cells to express antigen-specific CARs can provide a mechanism for targeted immune modulation, potentially restoring immune balance.
  4. Key Considerations: Factors such as optimal target cell populations, the design of CAR constructs, acceptable levels of toxicity, and the potential for a lasting immune reset are critical for the safe application of CAR T cell therapy in autoimmune diseases.

Key Results and Findings ​

  • Clinical trials targeting CD19 have yielded promising results, demonstrating the feasibility of CAR T cell therapy in treating B cell-driven autoimmune diseases.
  • The use of chimeric autoantibody receptors has shown potential in selectively depleting pathogenic B cells, thereby reducing disease symptoms.
  • Regulatory T cells engineered with antigen-specific CARs offer a novel strategy for modulating immune responses, highlighting a dual approach of both depletion and regulation.

Main Conclusions/Significance/Innovation ​

The study emphasizes the transformative potential of CAR T cell therapy in the realm of autoimmune diseases, which has traditionally been challenging to treat. The innovative approaches, including the development of chimeric autoantibody receptors and regulatory T cells, could lead to more effective and safer treatment options. The findings suggest that with careful consideration of target populations and construct design, CAR T cell therapy may pave the way for a new era in the management of autoimmune conditions.

Research Limitations and Future Directions ​

While the findings are promising, several limitations and future directions are noted:

  • Limitations: Current studies may have limited sample sizes and varying patient responses, necessitating larger, more diverse clinical trials to validate results.
  • Future Directions: Research should focus on optimizing CAR designs, understanding long-term effects, and exploring the application of CAR T cells in a broader range of autoimmune diseases. Additionally, strategies to mitigate potential toxicities and enhance patient safety will be crucial for the clinical adoption of these therapies.

In summary, the exploration of CAR T cell therapy for autoimmune diseases holds great promise, but further research is essential to fully realize its potential and ensure safe implementation in clinical practice.

References ​

  1. Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. - Jessica L Halliley;Christopher M Tipton;Jane Liesveld;Alexander F Rosenberg;Jaime Darce;Ivan V Gregoretti;Lana Popova;Denise Kaminiski;Christopher F Fucile;Igor Albizua;Shuya Kyu;Kuang-Yueh Chiang;Kyle T Bradley;Richard Burack;Mark Slifka;Erika Hammarlund;Hao Wu;Liping Zhao;Edward E Walsh;Ann R Falsey;Troy D Randall;Wan Cheung Cheung;Iñaki Sanz;F Eun-Hyung Lee - Immunity (2015)
  2. Fertility and CAR T-cells: Current practice and future directions. - John A Ligon;Abigail Fry;Jacqueline Y Maher;Toni Foley;Sara Silbert;Bonnie Yates;Veronica Gomez-Lobo;Lori Wiener;Nirali N Shah - Transplantation and cellular therapy (2022)
  3. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. - Tobias Alexander;Andreas Thiel;Oliver Rosen;Gero Massenkeil;Arne Sattler;Siegfried Kohler;Henrik Mei;Hartmut Radtke;Erika Gromnica-Ihle;Gerd-Rüdiger Burmester;Renate Arnold;Andreas Radbruch;Falk Hiepe - Blood (2009)
  4. Five-Year Outcomes for Refractory B-Cell Lymphomas with CAR T-Cell Therapy. - Elise A Chong;Marco Ruella;Stephen J Schuster; - The New England journal of medicine (2021)
  5. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. - Shannon L Maude;Theodore W Laetsch;Jochen Buechner;Susana Rives;Michael Boyer;Henrique Bittencourt;Peter Bader;Michael R Verneris;Heather E Stefanski;Gary D Myers;Muna Qayed;Barbara De Moerloose;Hidefumi Hiramatsu;Krysta Schlis;Kara L Davis;Paul L Martin;Eneida R Nemecek;Gregory A Yanik;Christina Peters;Andre Baruchel;Nicolas Boissel;Francoise Mechinaud;Adriana Balduzzi;Joerg Krueger;Carl H June;Bruce L Levine;Patricia Wood;Tetiana Taran;Mimi Leung;Karen T Mueller;Yiyun Zhang;Kapildeb Sen;David Lebwohl;Michael A Pulsipher;Stephan A Grupp - The New England journal of medicine (2018)
  6. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. - Michael Crump;Sattva S Neelapu;Umar Farooq;Eric Van Den Neste;John Kuruvilla;Jason Westin;Brian K Link;Annette Hay;James R Cerhan;Liting Zhu;Sami Boussetta;Lei Feng;Matthew J Maurer;Lynn Navale;Jeff Wiezorek;William Y Go;Christian Gisselbrecht - Blood (2017)
  7. Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis. - Xianghua Huang;Wencui Chen;Guisheng Ren;Liang Zhao;Jinzhou Guo;Dehua Gong;Caihong Zeng;Weixin Hu;Zhihong Liu - Clinical journal of the American Society of Nephrology : CJASN (2019)
  8. Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains. - Leah Alabanza;Melissa Pegues;Claudia Geldres;Victoria Shi;Jed J W Wiltzius;Stuart A Sievers;Shicheng Yang;James N Kochenderfer - Molecular therapy : the journal of the American Society of Gene Therapy (2017)
  9. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. - Adrienne H Long;Waleed M Haso;Jack F Shern;Kelsey M Wanhainen;Meera Murgai;Maria Ingaramo;Jillian P Smith;Alec J Walker;M Eric Kohler;Vikas R Venkateshwara;Rosandra N Kaplan;George H Patterson;Terry J Fry;Rimas J Orentas;Crystal L Mackall - Nature medicine (2015)
  10. Unanswered questions following reports of secondary malignancies after CAR-T cell therapy. - Bruce L Levine;Marcelo C Pasquini;John E Connolly;David L Porter;Michael P Gustafson;Jaap J Boelens;Edwin M Horwitz;Stephan A Grupp;Marcela V Maus;Frederick L Locke;Fabio Ciceri;Annalisa Ruggeri;John Snowden;Helen E Heslop;Crystal L Mackall;Carl H June;Anna M Sureda;Miguel-Angel Perales - Nature medicine (2024)

Literatures Citing This Work ​

  1. Advances in Juvenile Dermatomyositis: Pathophysiology, Diagnosis, Treatment and Interstitial Lung Diseases-A Narrative Review. - Ichiro Kobayashi - Children (Basel, Switzerland) (2024)
  2. Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome. - Jonathan Wickel;Ulf Schnetzke;Anne Sayer-Klink;Jenny Rinke;Dominic Borie;Diana Dudziak;Andreas Hochhaus;Lukas Heger;Christian Geis - Cell reports. Medicine (2024)
  3. Exploring structure-function relationships in engineered receptor performance using computational structure prediction. - William K Corcoran;Amparo Cosio;Hailey I Edelstein;Joshua N Leonard - bioRxiv : the preprint server for biology (2024)
  4. Chimeric antigen receptor T-cell therapy in autoimmune diseases. - Jie Liu;Yan Zhao;Hai Zhao - Frontiers in immunology (2024)
  5. Targeted degradation of membrane proteins. - Grace Hohman;Michael Shahid;Mohamed Eldeeb - Nature structural & molecular biology (2025)
  6. Past interactions of T cells with antigens shape CAR T cell responses. - Nature immunology (2025)
  7. Why is it so difficult to understand why we don't understand human systemic lupus erythematosus? Contemplating facts, conflicts, and impact of "the causality cascade paradigm". - Ole Petter Rekvig - Frontiers in immunology (2024)
  8. Monitoring the neurological complications of chimeric antigen receptor (CAR) T-cell therapy in patients with sensory and physical impairments and non-native-speaking backgrounds using modified immune effector cell-associated encephalopathy (ICE) scores: a case series. - Christina Kazzi;Ty Simpson;Cassandra Abbott;Miriam Wronski;Nabil Seery;Tracie Huey-Lin Tan;Robb Wesselingh;Katherine Ko;Shu Min Wong;Shafqat Inam;Constantine Tam;Shaun Fleming;Terence J O'Brien;Rubina Alpitsis;Andrew Spencer;Charles Malpas;Mastura Monif - BMJ neurology open (2025)
  9. Defining immune reset: achieving sustained remission in autoimmune diseases. - Tobias Junt;Thomas Calzascia;Elisabetta Traggiai;André Nogueira da Costa;Peter Gergely;Georg Schett;Thomas Dörner;Richard M Siegel - Nature reviews. Immunology (2025)
  10. Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics. - Xiaofeng Dai;Yuting Fan;Xing Zhao - Signal transduction and targeted therapy (2025)

... (14 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology