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Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.
Nat Cancer
January 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.
View Article and Find Full Text PDFIntracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.
Nat Med
January 2025
Seattle Children's Therapeutics, Seattle, WA, USA.
Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.
View Article and Find Full Text PDFSurvival benefit associated with liver transplantation for hepatocellular carcinoma based on tumor burden scores at listing.
Hepatol Commun
January 2025
Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Introduction: Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing.
View Article and Find Full Text PDFDendritic cells type 1 control the formation, maintenance, and function of tertiary lymphoid structures in cancer.
bioRxiv
December 2024
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood.
View Article and Find Full Text PDFTargeting CEA in metastatic triple negative breast cancer with image-guided radiation followed by Fab-mediated chimeric antigen receptor (CAR) T-cell therapy.
Front Immunol
January 2025
Department of Immunology and Theranostics, City of Hope, Duarte, CA, United States.
Introduction: Although CAR-T cell therapy has limited efficacy against solid tumors, it has been hypothesized that prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.
Methods: To test this hypothesis in a metastatic triple negative breast cancer (TNBC) model, we engineered two anti-CEA single-chain Fab (scFab) CAR-T cells with signaling domains from CD28zeta and 4-1BBzeta, and tested them and .
Results: The anti-CEA scFab CAR-T cells generated from three different human donors demonstrated robust expression, expansion, and lysis of only CEA-positive TNBC cells, with the CD28z-CAR-T cells showing the highest cytotoxicity.
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