CURRENT INDICATIONS IN CHILDREN AND PERSPECTIVES: Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease. Persistent remissions and even cures have been observed. These very good results could lead to use this treatment in first line for patients with very high-risk disease. However, CAR-T cells production, costs and adverse events management represent major issues for the future of this therapeutic. The occurrence of CD19 negative relapses has led to develop bispecific CAR-T cells. Allogeneic CAR would permit to obtain a "CAR garage" off the shelf available from the diagnosis. Perspectives for CAR-T cells are immense but will involve technological progresses around the CAR conception and production, leading to further improve results in leukemias (ALL but also AML) and lymphomas and hopefully to the emergence of efficacy in childhood solid tumors. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.
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http://dx.doi.org/10.1016/S0007-4551(19)30045-1 | DOI Listing |
Viruses
January 2025
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Gyeonggi-do, Republic of Korea.
Recent studies have highlighted that the microbiome is the essential factor that can modulate the clinical activity of immunotherapy. However, the role of the microbiome varies significantly across different immunotherapies, suggesting that it is critical to understand the precise function of the microbiome in each type of immunotherapy. While many previous studies primarily focus on summarizing the role of the microbiome in immune checkpoint inhibitors, we seek to explore a novel aspect of the microbiome in other immunotherapies such as mesenchymal stem cell therapy, chimeric antigen receptor T cell therapy, and antibodies-based therapy (e.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs).
View Article and Find Full Text PDFCancers (Basel)
January 2025
RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, 191144 St. Petersburg, Russia.
T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Division of Hematology and Medical Oncology, University of Washington, Seattle, WA 98195, USA.
Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on both agents. This subgroup of "double refractory" patients has limited treatment options and poor prognosis.
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