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| http://dx.doi.org/10.3389/fonc.2022.1026566 | DOI Listing |
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Targeting 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.
Prioritizing cases from a multi-institutional cohort for a dataset of pathologist annotations.
J Pathol Inform
January 2025
U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Imaging, Diagnostics, and Software Reliability, Silver Spring, MD, United States of America.
Objective: With the increasing energy surrounding the development of artificial intelligence and machine learning (AI/ML) models, the use of the same external validation dataset by various developers allows for a direct comparison of model performance. Through our High Throughput Truthing project, we are creating a validation dataset for AI/ML models trained in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC).
Materials And Methods: We obtained clinical metadata for hematoxylin and eosin-stained glass slides and corresponding scanned whole slide images (WSIs) of TNBC core biopsies from two US academic medical centers.
Correlation Between Disease-Free Survival Endpoints and Overall Survival in Elderly Patients with Early-Stage HER2-Negative Breast Cancer: A SEER-Medicare Analysis.
Adv Ther
December 2024
Merck & Co., Inc., 90 E Scott Ave, Rahway, NJ, 07065, USA.
Introduction: Recent trial-level meta-analyses have established disease-free survival (DFS) as a valid surrogate for overall survival (OS) in human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), irrespective of disease stage, and in early-stage hormone receptor-positive (HR+)/HER2- BC. To advance the understanding of the association between additional DFS endpoints and OS, this study assessed the patient-level correlations between DFS and OS, invasive DFS (IDFS) and OS, and distant DFS (DDFS) and OS in Medicare beneficiaries with early-stage HER2- BC, overall and in subgroups of patients with HR+/HER2- BC and triple-negative BC (TNBC).
Methods: Patients with stages I-III HER2- BC aged ≥ 66 years were identified from SEER-Medicare data (2010-2019).
Computational analysis of the functional impact of MHC-II-expressing triple-negative breast cancer.
Front Immunol
December 2024
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
Article Synopsis
- The tumor microenvironment (TME) is critical for tumor development and immune responses, with MHC-II playing a key role in immune surveillance.
- MHC-II is expressed not only by immune cells but also by tumor cells, particularly in triple-negative breast cancer (TNBC), which has a poor prognosis and limited treatments.
- A study identified a unique MHC-II-expressing tumor cell population that correlates with better patient outcomes and developed a prognostic gene signature to predict survival and immune infiltration, suggesting new therapeutic strategies.
Immunotherapy for Early-Stage Triple-Negative Breast Cancer.
N Engl J Med
November 2024
From Dana-Farber Cancer Institute, Harvard Medical School, Boston.
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