Chimeric antigen receptor T-cell (CAR-T) therapy, which has demonstrated notable efficacy against B-cell malignancies and is approved by the US Food and Drug Administration for clinical use in this context, represents a significant milestone in cancer immunotherapy. However, the efficacy of CAR-T therapy for the treatment of acute myeloid leukemia (AML) is poor. The challenges associated with the application of CAR-T therapy for the clinical treatment of AML include, but are not limited to, nonspecific distribution of AML therapeutic targets, difficulties in the production of CAR-T cells, AML blast cell heterogeneity, the immunosuppressive microenvironment in AML, and treatment-related adverse events. In this review, we summarize the recent findings regarding various therapeutic targets for AML (CD33, CD123, CLL1, CD7, etc.) and the results of the latest clinical studies on these targets. Thereafter, we also discuss the challenges related to CAR-T therapy for AML and some promising strategies for overcoming these challenges, including novel approaches such as gene editing and advances in CAR design.
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http://dx.doi.org/10.1177/20406207241263489 | 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
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 Stem Cell Transplant and Cellular Therapy, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USA.
Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and delayed issues like graft-versus-host disease (GVHD), infections, and secondary cancers. Effective management requires early diagnosis using advanced biomarkers and imaging, along with prompt interventions involving immunosuppressants, corticosteroids, and cytokine inhibitors.
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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