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Lipid-Rapamycin Nanovaccines Overcome the Antidrug Antibody Barrier in Biologic Therapies.
ACS Nano
January 2025
Wuya Faculty of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Antidrug antibodies (ADAs) against biologics present a major challenge for sustained biotherapy, including enzyme replacement therapies and adeno-associated virus (AAV) gene therapies. These antibodies arise from undesirable immune responses, leading to altered pharmacokinetics, reduced efficacy, and adverse reactions. In this study, we introduced a rationally designed lipid-rapamycin (Rapa)-based nanovaccine to restore immune tolerance to biologics and overcome drug resistance.
View Article and Find Full Text PDFSuccessful treatment of epidermal growth factor receptor exon 19 deletion non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: A case report.
J Cancer Res Ther
December 2024
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Shandong, China.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has revolutionized one of the standard most efficient treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently one of most efficient treatments in clinical practice. However, it has a potentially fatal side effect: interstitial lung disease (ILD).
View Article and Find Full Text PDFClozapine rechallenge following myocarditis: a systematic review of rechallenge cases.
CNS Spectr
December 2024
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Introduction And Objectives: Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.
View Article and Find Full Text PDFIntegrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function.
J Immunother Cancer
December 2024
Division of Genetic Immunotherapy, Leibniz Institute for Immunotherapy, Regensburg, Germany
Background: The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors indicating the need for adequately tuning CAR T cell functionality.
Methods: We leveraged a translational pipeline including biophysical characterization and structural prediction of the CAR binding moiety, evaluation of cellular avidity, synapse formation, T cell motility, and functional capacities under repetitive target challenge and in sustained tumor control.
Results: As an example of clinical relevance, we derived a panel of anti-Her2 CARs covering a 4-log affinity range, all expected to target the same Her2 epitope.
A novel mitochondrial pyruvate carrier inhibitor drives stem cell-like memory CAR T cell generation and enhances antitumor efficacy.
Mol Ther Oncol
December 2024
AGORA Cancer Research Center, 1005 Lausanne, Switzerland.
Adoptive cell transfer with chimeric antigen receptor (CAR)-expressing T cells can induce remarkable complete responses in cancer patients. Therapeutic success has been correlated with central and stem cell-like memory T cell subsets in the infusion product, which are better able to drive efficient CAR T cell expansion and long-term persistence. We previously reported that inhibition of the mitochondrial pyruvate carrier (MPC) during mouse CAR T cell culture induces a memory phenotype and enhances antitumor efficacy against melanoma.
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