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Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.
Cancer
February 2025
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, Maryland, USA.
Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).
View Article and Find Full Text PDFMechanisms for resistance to BCMA-targeted immunotherapies in multiple myeloma.
Blood Rev
January 2025
Department of Hematology, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:
Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined.
View Article and Find Full Text PDFReal-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.
Ann Hematol
December 2024
Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore, 168583, Singapore.
Background: Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity.
Methods: We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens.
Optimizing Siglec-8-Directed Immunotherapy for Eosinophilic and Mast Cell Disorders.
Cancers (Basel)
October 2024
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells.
View Article and Find Full Text PDFRapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology.
J Am Chem Soc
October 2024
Institut National de la Recherche Scientifique (INRS), EMT Research Center, Varennes, Quebec J3X 1P7, Canada.
Bispecific antibodies (bsAbs) are emerging immune-therapeutics, and many formats exist that differ considerably in structure. However, little systematic data exist about how the spatial organization of their components influences activity, requiring innovative approaches combining empirical and quantitative frameworks. This study presents a modular DNA nanotechnology platform to generate numerous bsAbs with surrogate geometries that span the structural features of the BiTE, IgG-like, and IgG-conjugate platforms to screen for T-cell engagement.
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