Isolation of circulating tumor cells (CTCs) from blood provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancer. The roles and clinical values of CTCs are under intensive investigation, yet most studies are limited by technical challenges in the comprehensive enrichment of intact and viable CTCs with minimal white blood cell (WBC) contamination. Here, we report a novel method based on contrast of cell magnetization in biocompatible ferrofluids (a colloidal magnetic nanoparticle suspension), termed as integrated ferrohydrodynamic cell separation (iFCS), that enriches CTCs in a tumor antigen-independent and cell size variation-inclusive manner, achieves a high throughput (12 mL h-1), high recovery rate (99.08% at down to ∼10 cells per mL spike ratio), and low WBC contamination (533 cells for every one milliliter blood processed) and is biocompatible. This method will enable large cohort research to define the clinical and diagnostic value of CTC subtypes.
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http://dx.doi.org/10.1039/c9lc00210c | DOI Listing |
Int J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
View Article and Find Full Text PDFFront Immunol
December 2024
Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.
The development of T cell receptor-engineered T cells (TCR-T) targeting intracellular antigens is a promising strategy for treating solid tumors; however, the mechanisms underlying their effectiveness remain poorly understood. In this study, we employed advanced techniques to investigate the functional state of T cells engineered with retroviral vectors to express a TCR specific for the NY-ESO-1 157-165 peptide in the HLA-A*02:01 context. Flow cytometry revealed a predominance of naïve T cells.
View Article and Find Full Text PDFJ 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.
Biosens Bioelectron
March 2025
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Center for Wireless Integrated MicroSensing and Systems (WIMS(2)), University of Michigan, Ann Arbor, MI, 48109, USA; Max Harry Weil Institute for Critical Care Research and Innovation, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:
Circulating tumor cells (CTCs) in the bloodstream are important biomarkers for clinical prognosis of cancers. Current CTC identification methods are based on immuno-labeling, which depends on the differential expression of specific antigens between the cancer cells and white blood cells. Here we present an antigen-independent CTC detection method utilizing a deep-learning-assisted single-cell biolaser.
View Article and Find Full Text PDFJ Immunother Cancer
October 2024
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China
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