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Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study.
Clin Lung Cancer
January 2025
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Background: Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.
Methods: This retrospective study included patients with advanced nonsquamous NSCLC with a PD-L1 tumor proportion score of 1% to 49% administered ICI combination platinum-based chemotherapy between May 2018 and May 2023 at 19 institutions in Japan.
Ethiodized Oil Pickering Emulsion for Sustained Release of Anti-PD-L1 Antibodies.
J Vasc Interv Radiol
January 2025
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine. 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Purpose: This research aimed to develop and assess a Lipiodol Pickering emulsion containing anti-Programmed cell Death Ligand 1 (PD-L1) antibodies through in vitro experiments.
Materials And Methods: The emulsion was created by combining Lipiodol with poly (lactic-co-glycolic acid) (PLGA) nanoparticles and anti-PD-L1 antibodies. Confocal laser microscopy was used to evaluate the encapsulation of the antibodies within the Pickering emulsion.
Neoadjuvant anti-PD-1-based immunotherapy: evolving a new standard of care.
J Immunother Cancer
January 2025
The Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, Maryland, USA.
Neoadjuvant (presurgical) anti-programmed cell death protein-1 (PD-1)-based immunotherapy as a new approach to cancer treatment has been developing on an accelerated trajectory since the seminal clinical trial results from studies in lung cancer and melanoma were published in 2018. Groundbreaking regulatory approvals in triple-negative breast cancer, non-small cell lung cancer and melanoma will certainly be followed by additional approvals in other disease indications, as clinical and basic research are burgeoning globally in hundreds of clinical trials across dozens of cancer types. As this field is evolving, it is addressing gaps in our understanding of biological mechanisms underlying PD-1 pathway blockade and their synergy with other antineoplastic drugs, probing mechanisms of response and resistance to neoadjuvant immunotherapy, optimizing efficacious clinical strategies, and analyzing commonalities and differences across cancer types.
View Article and Find Full Text PDFThe cyclin-dependent kinase inhibitor AT7519 is a human RORγt agonist.
Immunol Cell Biol
January 2025
Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland.
AT7519, which inhibits multiple cyclin-dependent kinases, has been extensively investigated in various types of cancer cells. Previous studies have demonstrated the ability of this molecule to suppress the expression of the nuclear receptor retinoic acid-related orphan receptor gamma (RORγ) and several genes involved in hepatocellular carcinoma progression. In this study, we identified a distinct agonistic effect of AT7519 on RORγt, an isoform expressed by various immune cells, including T helper 17 lymphocytes.
View Article and Find Full Text PDFA phase 2 basket study of talabostat, a small-molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers.
Cancer
February 2025
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.
Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.
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