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Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers.
Oncoimmunology
December 2025
Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre, Madrid, Spain.
Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments.
View Article and Find Full Text PDFFrom promise to practice: CAR T and Treg cell therapies in autoimmunity and other immune-mediated diseases.
Front Immunol
December 2024
Department of Research and Development, Tr1X, Inc., San Diego, CA, United States.
Autoimmune diseases, characterized by the immune system's attack on the body's own tissues, affect millions of people worldwide. Current treatments, which primarily rely on broad immunosuppression and symptom management, are often associated with significant adverse effects and necessitate lifelong therapy. This review explores the next generation of therapies for immune-mediated diseases, including chimeric antigen receptor (CAR) T cell and regulatory T cell (Treg)-based approaches, which offer the prospect of targeted, durable disease remission.
View Article and Find Full Text PDFPost-CAR T-Cell Therapy Failure Metabolic Parameters Predict Survival and Response in Large B-Cell Lymphoma.
Hematol Oncol
January 2025
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters have shown a significant prognostic role in relapsed/refractory large B-cell lymphoma (LBCL) patients undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. While a substantial body of evidence exists on the prognostic value of PET/CT parameters in peri-CAR T setting, data available on the prognostic value of PET/CT parameters following CAR T-cell therapy failure is lacking. Therefore, we sought to analyze the PET/CT scans of LBCL patients who experienced post-CAR T relapsed/progressive disease and subsequently received salvage therapies.
View Article and Find Full Text PDFAdvances in CD19-targeting CAR-T cell therapies for multiple myeloma.
Expert Opin Biol Ther
January 2025
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
Introduction: Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention.
Areas Covered: This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM.
Identifying CD19-targeted CAR-T cell immune pathways in an in vitro human immune mimetic cytokine release assay.
J Immunotoxicol
October 2024
Sanofi, Global Human Immunology, Orlando, FL, USA.
CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells have shown success in clinical studies, with several CD19 CAR-T cell products now having been approved for market use. However, this cell therapy can be associated with side effects such as cytokine release syndrome (CRS). Therefore, pre-clinical test systems are highly desired to permit the evaluation of these unwanted effects before clinical trials begin.
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