A5024549907- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Prostate Cancer Treatment and Research
- Cancer, Stress, Anesthesia, and Immune Response
- Chemokine receptors and signaling
- Medical Imaging Techniques and Applications
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Advanced biosensing and bioanalysis techniques
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Lung Cancer Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Radiopharmaceutical Chemistry and Applications
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Single-cell and spatial transcriptomics
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
- Chromosomal and Genetic Variations
- Lymphoma Diagnosis and Treatment
- Cancer Treatment and Pharmacology
Johnson & Johnson (United States)
2020-2025
Janssen (United States)
2013-2023
Springhouse
2015-2020
Pacific Biomarkers (United States)
2016
Duke Medical Center
2016
University of Twente
2011
We describe two patients in whom malignant monoclonal T-cell lymphoproliferation developed after administration of chimeric antigen receptor (CAR) therapy with ciltacabtagene autoleucel (cilta-cel) the phase 3 CARTITUDE-4 trial. Monoclonal T cells from both had detectable CAR transgene expression and integration. The clinicogenomic features these transgenic lymphoproliferative neoplasms suggest that multiple potential intrinsic or extrinsic factors (or both) contributed to their...
Abstract CD38-targeted antibody, daratumumab, is approved for the treatment of multiple myeloma (MM). Phase 1/2 studies GEN501/SIRIUS revealed a novel immunomodulatory mechanism action (MOA) daratumumab that enhanced immune response, reducing natural killer (NK) cells without affecting efficacy or safety. We further evaluated daratumumab’s effects on in whole blood samples relapsed/refractory MM patients from both arms phase 3 POLLUX study (lenalidomide/dexamethasone [Rd] plus Rd [D-Rd]) at...
BACKGROUND Two androgen receptor (AR)‐targeted therapies, enzalutamide and abiraterone acetate plus prednisone (abiraterone), have been approved for the treatment of metastatic castration‐resistant prostate cancer (CRPC). Many patients respond to these agents, but both de novo acquired resistance are common. The authors characterized resistant phenotypes that emerge after with or enzalutamide. METHODS Patients who received in course routine clinical care were consented serial blood...
Summary We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression genes characteristic fluorescence in situ hybridisation results on correlated well bone marrow results. enumerated over 1000 patient samples including separate cohorts newly diagnosed high/intermediate risk smouldering (SMM) clinical follow‐up data. In samples, counts other measures disease...
Abstract CD33 is expressed in 90% of patients with acute myeloid leukemia (AML), and its extracellular portion consists a V domain C2 domain. A recent study showed that single nucleotide polymorphism (SNP), rs12459419 (C > T), results the reduced expression domain–containing limited efficacy domain–binding anti-CD33 antibodies. We developed JNJ-67571244, novel human bispecific antibody capable binding to CD3, induce T-cell recruitment CD33+ tumor cell cytotoxicity independently their...
Abstract Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture characterize circulating tumor cells (CTC) expressing c-MET using ferromagnetic antibody. Immunofluorescence was used for c-MET, DAPI, pan-CK, excluding CD45+ leukocytes. The assay validated appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, analyzed...
FISH probes are generally made out of BAC clones with genomic DNA containing a variable amount repetitive that will need to be removed or blocked for analysis. To generate repeat free (RF) Probes without loss in coverage, random library is from by whole-genome amplification (WGA). Libraries denatured the presence excess C(0)t-1 and allowed re-anneal followed digestion all double-stranded elements duplex-specific nuclease (DSN). Selective not sequences realized sequential amplification. The...
e16529 Background: Prostate cancer is the most common in men U.S., with 30% 5-year overall survival (OS) for patients (pts) metastases. To take a precision medicine approach to management of metastatic castrate-resistant prostate (mCRPC), we developed blood circulating tumor cell (CTC)-based test identify mCRPC pts likely benefit from abiraterone (abi) or enzalutamide (enza). Methods: In this multi-institution prospective study, were enrolled prior starting abi (1,000 mg/d plus prednisone 10...
Abstract There is an increasing interest in the ability to dynamically track disease burden and perform molecular subtyping of patients with plasma cell disorders without invasive bone marrow sampling. Circulating multiple myeloma cells (CMMC) have been detected elevated numbers peripheral blood using flow cytometry or circulating enrichment platforms. We developed automated CELLSEARCH® assay enrich, enumerate, a triplex FISH for t(4;14), t(14;16), del 17p on CMMC (CD138+CD38+, CD45-CD19-)...
84 Background: Multiple GI malignancies including gastric, pancreatic, and colorectal cancers harbor genetic alterations in the MET oncogene. amplification is associated with poor prognosis, c-MET targeted therapies are development. We aimed to capture identify CTCs using a non-invasive, rapid test. Methods: modified CELLSEARCH platform by nanomagnetic particles conjugated antibodies against extracellular domain of c-MET-expressing CTCs. The method was validated spiking MET-amplified gastric...
Abstract CD33 is expressed in 90% of acute myeloid leukemia (AML) patients with expression both blasts and leukemic stem cells. The extracellular portion consists a V C2 Ig-like domain. A recent study showed that single nucleotide polymorphism (SNP) rs12459419 (C >T; Ala14Val exon 2 CD33) was present ~50% the Western AML population associated preferential an alternatively spliced isoform lacking exon2, resulting deletion Interestingly, several CD33-antibody-based therapies, including...
Abstract Background: Numbers of circulating tumor cells (CTC) measured with the CellSearch system in patients metastatic carcinomas are associated poor survival. Such association clinical outcome suggests that CTCs play an important role process. Molecular characterization can provide insights into phenotypic characteristics necessary to participate this Moreover, detailed molecular at various points disease course may be useful understanding evolution tumors and aid selection optimal...
Abstract Multiple Myeloma is bone marrow tumor that frequently results in the aberrant release of neoplastic plasma cells into circulation. The CELLSEARCH® system (Janssen Diagnostics, Raritan, NJ) has been used to capture, enumerate, and perform FISH analysis on circulating multiple myeloma (CMMC) from patients with active myeloma, smoldering MGUS (Gross, et.al. Poster #1825, ASH 2011). This method utilizes a blood fixative subsequently permeabilizes cells, which confounds ability do mRNA...
Abstract Despite the introduction of a number new treatment options (such as abiraterone acetate and enzalutamide) for castration resistant prostate cancer (CRPC), patients with this disease eventually progress. In order to understand how help such patients, it is paramount biological characteristics that emerges in response lines therapy. Unfortunately, repeat biopsy samples are difficult attain may not reflect full complexity disease. Circulating tumor cells (CTCs) provide powerful...
11024 Background: Genetic alterations in the MET oncogene exist many GI and GU malignancies. amplification is associated with poor prognosis can arise as a resistance mechanism to EGFR targeting therapies. We aimed capture identify CTCs expressing c-MET. Methods: modified Cellsearchplatform by using nanomagnetic particles conjugated antibodies against c-MET c-MET-expressing stained for c-MET-PE, DAPI, pan-CK-FITC. CD45 + cells were excluded. The method was validated spiking MET-amplified...
e16032 Background: Response and resistance to AA may involve AR splice variants (ARVs) other biomarkers. We developed a CTC axis panel explored the association between biomarkers response in 2 phase trials Japanese mCRPC pts. Methods: 95 pts with (n = 47) or without prior chemotherapy 48) were included. Primary end point: proportion of prostate-specific antigen (PSA) (≥ 50% decline from baseline) by 12 weeks. Pretreatment samples processed for enumeration; protein staining; characterization...
Abstract Circulating tumor cells (CTCs) of epithelial origin are present in the blood carcinoma patients at very low frequency (< 10 / ml blood). In order to characterize CTCs, they need be enriched from large volumes (7.5 mLs). The CELLSEARCH® Tumor Cell (Epithelial) assay uses magnetic particles conjugated anti-epithelial cell adhesion molecule (EpCAM) selectively capture CTCs. After enrichment, sample contains CTCs and a number (1000 - 5000) white (WBCs). presence WBCs CTC may...
<p>Immunofluorescence characterization of EpCAM and c-MET in cell lines. Immunofluorescence SNU5, HeLa SIHA lines, with (clockwise from top left each panel) external c-MET, EpCAM, DAPI slide, slide.</p>