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CAR T-Cell Therapy in Hematologic Malignancies: A Voyage in Progress. ​

Literature Information ​

DOI10.1002/cpt.1674
PMID31622496
JournalClinical pharmacology and therapeutics
Impact Factor5.5
JCR QuartileQ1
Publication Year2020
Times Cited95
KeywordsCAR T-cell therapy, hematologic malignancies, CD19-targeted, multiple myeloma, B-cell maturation antigen
Literature TypeJournal Article, Review
ISSN0009-9236
Pages112-122
Issue107(1)
AuthorsSarah A Holstein, Matthew A Lunning

TL;DR ​

This paper discusses the advancements in chimeric antigen receptor (CAR) T-cell therapy, particularly the success of CD19-targeted therapies for hematological cancers like diffuse large B-cell lymphoma and acute lymphoblastic leukemia, and highlights ongoing research into B-cell maturation antigen-directed therapies for multiple myeloma. It underscores the challenges that remain in optimizing CAR T-cell therapy and the importance of exploring new targets and methods to enhance treatment efficacy in various hematological malignancies.

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CAR T-cell therapy · hematologic malignancies · CD19-targeted · multiple myeloma · B-cell maturation antigen

Abstract ​

The development of chimeric antigen receptor (CAR) T-cell therapy for select hematological malignancies represents one of the most remarkable therapeutic advances in the past decade. Currently, CD19-targeted CAR T-cell therapy is approved for relapsed/refractory diffuse large B-cell lymphoma and acute lymphoblastic leukemia. However, there is significant interest in the application of CAR T-cell therapy to other hematological malignancies, including multiple myeloma, where the current focus is on the development of B-cell maturation antigen-directed CAR T-cell therapy. Despite the successes achieved to date, there remain significant challenges associated with CAR T-cell therapy and substantial research efforts are underway to develop new targets and approaches. Here, we provide an overview of the rapidly evolving landscape of CAR T-cell therapy in hematological malignancies and look ahead at the advances that will shape the future of this field.

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Primary Questions Addressed ​

  1. What are the potential benefits of expanding CAR T-cell therapy beyond CD19-targeted treatments in hematological malignancies?
  2. How does the development of B-cell maturation antigen-directed CAR T-cell therapy differ from existing CAR T-cell therapies?
  3. What specific challenges are researchers facing in the application of CAR T-cell therapy to multiple myeloma?
  4. In what ways might new targets and approaches in CAR T-cell therapy impact patient outcomes in hematological malignancies?
  5. What future advancements in CAR T-cell therapy are anticipated to address the current limitations and enhance treatment efficacy?

Key Findings ​

Key Insights on CAR T-Cell Therapy in Hematologic Malignancies

  1. Research Background and Purpose: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking treatment modality for certain hematological malignancies over the past decade. The primary focus of this therapy has been on its application for relapsed/refractory diffuse large B-cell lymphoma and acute lymphoblastic leukemia, both of which present significant treatment challenges. The purpose of the study is to provide a comprehensive overview of the advancements in CAR T-cell therapy, particularly its current utilization and potential future applications in various hematologic malignancies, with a specific emphasis on emerging targets like B-cell maturation antigen in multiple myeloma.

  2. Major Methods and Findings: The study synthesizes recent advancements in CAR T-cell technology and its clinical applications. It highlights the approval of CD19-targeted CAR T-cell therapy and discusses ongoing research into other targets, including B-cell maturation antigen for multiple myeloma. The findings underscore the progress made in tailoring CAR T-cell therapy to different malignancies, alongside the identification of challenges such as cytokine release syndrome, neurotoxicity, and the need for improving the persistence and efficacy of CAR T-cells. The exploration of novel targets and innovative approaches forms a significant part of ongoing research efforts aimed at expanding the effectiveness of CAR T therapies.

  3. Core Conclusions: The development of CAR T-cell therapy has revolutionized the treatment landscape for certain hematological malignancies, showcasing remarkable success in specific patient populations. However, the therapy is not without its challenges, which necessitate continued research and development. The study concludes that while progress is noteworthy, the future of CAR T-cell therapy will depend on overcoming existing barriers and expanding the repertoire of targets beyond currently approved indications.

  4. Research Significance and Impact: This research has substantial significance for the field of oncology, particularly in hematological malignancies, as it informs clinicians and researchers about the current state and future directions of CAR T-cell therapy. The insights provided can guide the development of more effective treatments, potentially increasing the number of patients who can benefit from CAR T approaches. By addressing the challenges and exploring new targets, the field can advance toward more personalized and effective cancer therapies, ultimately improving patient outcomes and survival rates in hematologic cancers. The work emphasizes the need for collaborative efforts in research and clinical practice to navigate the evolving landscape of CAR T-cell therapy.

Literatures Citing This Work ​

  1. Long-Term Follow-up of CALGB (Alliance) 100001: Autologous Followed by Nonmyeloablative Allogeneic Transplant for Multiple Myeloma. - Sarah A Holstein;Vera J Suman;Kouros Owzar;Katelyn Santo;Don M Benson;Thomas C Shea;Thomas Martin;Margarida Silverman;Luis Isola;Ravi Vij;Bruce D Cheson;Charles Linker;Kenneth C Anderson;Paul G Richardson;Philip L McCarthy - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2020)
  2. Identifying and Targeting Human Tumor Antigens for T Cell-Based Immunotherapy of Solid Tumors. - Vid Leko;Steven A Rosenberg - Cancer cell (2020)
  3. CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality? - Jessica Wagner;Elizabeth Wickman;Christopher DeRenzo;Stephen Gottschalk - Molecular therapy : the journal of the American Society of Gene Therapy (2020)
  4. EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer. - Jing-Tao Zhou;Jiang-Hao Liu;Ting-Ting Song;Bo Ma;Nuermaimait Amidula;Chao Bai - Cancer management and research (2020)
  5. A soluble activator that favors the ex vivo expansion of CD8+CD27+ T cells. - Esther I Matus;Amanda Sparkes;Jean Gariépy - JCI insight (2020)
  6. Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies. - Wen-Ying Lin;Hsin-Hui Wang;Yi-Wei Chen;Chun-Fu Lin;Hueng-Chuen Fan;Yi-Yen Lee - International journal of molecular sciences (2020)
  7. Adoptive T cell therapy: Boosting the immune system to fight cancer. - Ernesto Leon;Raghuveer Ranganathan;Barbara Savoldo - Seminars in immunology (2020)
  8. Extending the Promise of Chimeric Antigen Receptor T-Cell Therapy Beyond Targeting CD19+ Tumors. - Natalie S Grover;Nicholas Tschernia;Gianpietro Dotti;Barbara Savoldo - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021)
  9. Gut microbiota: impacts on gastrointestinal cancer immunotherapy. - Harry Cheuk Hay Lau;Joseph Jao-Yiu Sung;Jun Yu - Gut microbes (2021)
  10. Patient-Reported Outcomes for Cancer Patients with Hematological Malignancies Undergoing Chimeric Antigen Receptor T Cell Therapy: A Systematic Review. - Mona Kamal;Jacinth Joseph;Uri Greenbaum;Rachel Hicklen;Partow Kebriaei;Samer A Srour;Xin Shelly Wang - Transplantation and cellular therapy (2021)

... (85 more literatures)

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