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| http://dx.doi.org/10.3324/haematol.2023.284917 | DOI Listing |
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Population Pharmacokinetics of Orvacabtagene Autoleucel, an Autologous BCMA-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed/Refractory Multiple Myeloma.
Clin Cancer Res
January 2025
Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).
Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.
Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach.
J Transl Med
January 2025
Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.
View Article and Find Full Text PDFIncidence of Acute Kidney Injury in Relapsed and Refractory Multiple Myeloma treated with Teclistamab versus CAR T-cells.
Nephrol Dial Transplant
January 2025
Division of Nephrology and Hypertension, Rochester, MN, USA.
Background And Hypothesis: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B-cell maturation antigen (BCMA), and chimeric antigen receptor T-cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy.
View Article and Find Full Text PDFOptimized BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21 robustly control multiple myeloma.
Front Immunol
January 2025
Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Introduction: Challenges remain in reducing antigen escape and tumor recurrence while CAR-T cell therapy has substantially improved outcomes in the treatment of multiple myeloma. T cell receptor fusion construct (TRuC)-T cells, which utilize intact T cell receptor (TCR)-CD3 complex to eliminate tumor cells in a non-major histocompatibility complex (MHC)-restricted manner, represent a promising strategy. Moreover, interleukin-7 (IL-7) is known to enhance the proliferation and survival of T cells.
View Article and Find Full Text PDFComprehensive Review of Bispecific Antibody Constructs In Multiple Myeloma: Affinities, Dosing Strategies and Future Perspectives.
Clin Lymphoma Myeloma Leuk
November 2024
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. Electronic address:
Despite significant advancements, multiple myeloma (MM) remains incurable, and there is still a pressing need for new therapeutic strategies with highly selective mechanisms of action and balanced off-target toxicity. In recent years, the development of "off-the-shelf" bispecific antibodies (bsAbs) has significantly enhanced our ability to treat relapsed or refractory MM. Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
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