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Curated Papers > Highly Cited Authoritative Literature on CAR-T Therapy

CAR T cell immunotherapy for human cancer. ​

Literature Information ​

DOI10.1126/science.aar6711
PMID29567707
JournalScience (New York, N.Y.)
Impact Factor45.8
JCR QuartileQ1
Publication Year2018
Times Cited1450
KeywordsCAR T cell immunotherapy, tumor, lymphoma, antitumor, immuno-oncology
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Review
ISSN0036-8075
Pages1361-1365
Issue359(6382)
AuthorsCarl H June, Roddy S O'Connor, Omkar U Kawalekar, Saba Ghassemi, Michael C Milone

TL;DR ​

This review highlights the rapid advancement of adoptive T cell transfer (ACT) in transfusion medicine, particularly the commercialization of chimeric antigen receptor (CAR) T cells for leukemia and lymphoma treatment. It discusses the current opportunities and challenges that the CAR T field faces in becoming a mainstream approach in oncology, emphasizing emerging obstacles in recent years.

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CAR T cell immunotherapy · tumor · lymphoma · antitumor · immuno-oncology

Abstract ​

Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, with a focus on the challenges that have emerged over the past several years.

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Primary Questions Addressed ​

  1. What are the specific challenges faced by CAR T cell therapy in treating solid tumors compared to hematological malignancies?
  2. How do the mechanisms of action of CAR T cells differ from traditional chemotherapy and radiation therapies in cancer treatment?
  3. What advancements in CAR T cell technology could enhance their effectiveness and safety in a broader range of cancers?
  4. In what ways could the integration of CAR T cell therapy with other immunotherapies improve patient outcomes?
  5. What role does patient selection play in the success of CAR T cell therapies, and how can biomarkers be used to optimize treatment strategies?

Key Findings ​

Key Insights ​

  1. Research Background and Objectives: The field of adoptive T cell transfer (ACT) has emerged as a promising strategy in transfusion medicine, focusing on the infusion of lymphocytes to elicit antitumor, antiviral, or anti-inflammatory effects. The primary objective of this research is to explore the advancements made in CAR T cell immunotherapy, particularly regarding its transition from preclinical models to successful commercial applications for treating hematological malignancies such as leukemia and lymphoma. The Review aims to identify both the opportunities and challenges the CAR T cell field faces as it seeks to integrate more fully into mainstream oncology.

  2. Key Methods and Findings: The Review synthesizes current literature and clinical findings related to CAR T cell therapy, detailing the mechanisms by which these engineered T cells target specific cancer antigens. It discusses the rapid advancements leading to the FDA's approval of CAR T therapies, highlighting the successful clinical outcomes observed in certain patient populations. However, the article also addresses significant challenges, including the management of adverse effects like cytokine release syndrome and neurotoxicity, the accessibility of treatments to diverse patient populations, and the high costs associated with CAR T cell production and administration.

  3. Core Conclusions: The Review concludes that while CAR T cell immunotherapy has shown remarkable success in certain blood cancers, significant hurdles remain before it can be widely adopted in broader oncology settings. The challenges identified—ranging from safety and efficacy concerns to economic and logistical barriers—must be addressed to improve patient access and treatment outcomes. Additionally, the need for more research into the long-term effects and potential applications of CAR T therapies for solid tumors is emphasized.

  4. Research Significance and Impact: This Review underscores the transformative potential of CAR T cell immunotherapy in cancer treatment, signifying a paradigm shift in how certain malignancies are approached. By identifying both the promise of CAR T approaches and the critical challenges that need addressing, the research advocates for a multifaceted strategy involving continued innovation, collaborative research efforts, and policy changes to facilitate broader implementation. The insights presented can inform future studies and clinical practices, ultimately aiming to enhance therapeutic efficacy and accessibility in oncology, thereby improving patient outcomes across diverse cancer types.

Literatures Citing This Work ​

  1. Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis. - Leslie S Kean - Blood (2018)
  2. Immune therapies in pancreatic ductal adenocarcinoma: Where are we now? - Marc Hilmi;Laurent Bartholin;Cindy Neuzillet - World journal of gastroenterology (2018)
  3. Immunotherapy of Primary Brain Tumors: Facts and Hopes. - Robin A Buerki;Zinal S Chheda;Hideho Okada - Clinical cancer research : an official journal of the American Association for Cancer Research (2018)
  4. Macrophage targeting: opening new possibilities for cancer immunotherapy. - Luca Cassetta;Takanori Kitamura - Immunology (2018)
  5. Chimeric Antigen Receptor Therapy. - Carl H June;Michel Sadelain - The New England journal of medicine (2018)
  6. Current status of immunotherapy against gastrointestinal cancers and its biomarkers: Perspective for precision immunotherapy. - Shoichi Hazama;Koji Tamada;Yoshiyuki Yamaguchi;Yutaka Kawakami;Hiroaki Nagano - Annals of gastroenterological surgery (2018)
  7. Cancer immune therapy for lymphoid malignancies: recent advances. - Uffe Klausen;Nicolai Grønne Dahlager Jørgensen;Jacob Handlos Grauslund;Morten Orebo Holmström;Mads Hald Andersen - Seminars in immunopathology (2019)
  8. CAR T cells for infection, autoimmunity and allotransplantation. - Colby R Maldini;Gavin I Ellis;James L Riley - Nature reviews. Immunology (2018)
  9. Immunogenomics Analysis Reveals that TP53 Mutations Inhibit Tumor Immunity in Gastric Cancer. - Zehang Jiang;Zhixian Liu;Mengyuan Li;Cai Chen;Xiaosheng Wang - Translational oncology (2018)
  10. Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life. - Michelle Miron;Brahma V Kumar;Wenzhao Meng;Tomer Granot;Dustin J Carpenter;Takashi Senda;Dora Chen;Aaron M Rosenfeld;Bochao Zhang;Harvey Lerner;Amy L Friedman;Uri Hershberg;Yufeng Shen;Adeeb Rahman;Eline T Luning Prak;Donna L Farber - Journal of immunology (Baltimore, Md. : 1950) (2018)

... (1440 more literatures)

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