A5027870555- Biomarkers in Disease Mechanisms
- Autophagy in Disease and Therapy
- Circular RNAs in diseases
- Extracellular vesicles in disease
- RNA modifications and cancer
- CAR-T cell therapy research
- Neuroblastoma Research and Treatments
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Cell death mechanisms and regulation
- Advancements in Semiconductor Devices and Circuit Design
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Cardiac tumors and thrombi
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Acute Myeloid Leukemia Research
Century Therapeutics (United States)
2024
Pennsylvania State University
2014-2023
Cancer Genetics (United States)
2020-2023
National Cancer Institute
2020-2023
National Institutes of Health
2023
Center for Cancer Research
2021-2023
Penn State Milton S. Hershey Medical Center
2016-2020
Pediatrics and Genetics
2020
Hershey (United States)
2014
Chimeric antigen receptor (CAR) T cell therapies targeting single antigens have performed poorly in clinical trials for solid tumors due to heterogenous expression of tumor-associated (TAAs), limited persistence, and exhaustion. Here, we aimed identify optimal CARs against glypican 2 (GPC2) or CD276 (B7-H3), which were highly but heterogeneously expressed neuroblastoma (NB), a lethal extracranial tumor childhood. First, examined CAR expansion the presence targets by digital droplet PCR....
Abstract Neuroblastoma is the most common extracranial solid malignancy in pediatric population, accounting for over 9% of all cancer-related deaths children. Autophagy a cell self-protective mechanism that promotes tumor growth and survival, making it an attractive target treating cancer. However, role autophagy neuroblastoma metastasis largely undefined. Here we demonstrate targeted inhibition essential kinase, unc-51 like kinase 1 (ULK1), with recently developed small-molecule inhibitor...
Abstract Although neoadjuvant chemotherapy is a standard component of breast cancer treatment, recent evidence suggests that chemotherapeutic drugs can promote metastasis through poorly defined mechanisms. Here we utilize xenograft mouse models triple-negative to explore the importance chemotherapy-induced tumor-derived small extracellular vesicles (sEV) in metastasis. Doxorubicin (DXR) enhanced tumor cell sEV secretion accelerate pulmonary by priming premetastatic niche. Proteomic analysis...
Targeting solid tumors must overcome several major obstacles, in particular, the identification of elusive tumor-specific antigens. Here, we devise a strategy to help identify epitopes. Glypican 2 (GPC2) is overexpressed neuroblastoma. Using RNA sequencing (RNA-seq) analysis, show that exon 3 and exons 7-10 GPC2 are expressed cancer but minimally normal tissues. Accordingly, discover monoclonal antibody (CT3) binds 10 visualize complex structure CT3 by electron microscopy. The potential this...
CD276/B7-H3 represents a promising target for cancer therapy based on widespread overexpression in both cells and tumor-associated stroma. In previous preclinical studies, CD276 antibody-drug conjugates (ADCs) exploiting talirine-type pyrrolobenzodiazepine (PBD) payload showed potent activity against various solid tumors but with narrow therapeutic index dosing regimen higher than that tolerated clinical trials using other antibody-talirine conjugates. Here, we describe the development of...
Abstract Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored impact autophagy on pathophysiology breast using a novel hypoxia-dependent, reversible dominant-negative strategy regulate at cellular level within TME. Suppression via hypoxia-induced expression kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in MDA-MB-231 xenograft...
Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified natural product marinopyrrole A (maritoclax) as novel small molecule Mcl-1 inhibitor. Here, we describe structure-activity relationship study pyoluteorin derivatives based on maritoclax. To date, synthesized over 30 maritoclax and evaluated their inhibitory actions cytotoxicity toward Mcl-1-dependent cell lines. As result, several functional groups were in motif...
Abstract Century Therapeutics is developing NECTIN4 targeted induced Pluripotent Stem Cell (iPSC) derived Chimeric Antigen Receptor (CAR) T cell therapy. antibody drug conjugate enfortumab vedotin, while generally well tolerated, causes severe skin adverse events in some patients, thought to be driven by on-target off-tumor toxicity against displaying keratinocytes. We include a safety switch our first clinical-stage iPSC-derived CAR-NK therapy, CNTY-101, which provides an target for...
Abstract Single domain antibodies have certain advantages including their small size, high stability and excellent tissue penetration, making them attractive drug candidates. Rabbit can recognize diverse epitopes, those that are poorly immunogenic in mice humans. In the present study, we established a method to isolate rabbit VH single for potential cancer therapy. We immunized rabbits with recombinant human B7-H3 (CD276) protein, made phage-displayed library diversity of 7 × 109, isolated...
Abstract The tumor microenvironment (TME) is a complex and dynamic breeding ground for the selection of aggressive cells with an advantage survival metastatic potential. Autophagy has emerged as powerful cellular process that can greatly influence how cancer respond to nutrient deprivation hypoxic stress, hallmarks TME. However, physiological importance hypoxia-regulated autophagy remains unknown. Here, we used novel hypoxia-dependent reversible dominant-negative strategy, which allowed...
<div>Abstract<p>Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored impact autophagy on pathophysiology breast using a novel hypoxia-dependent, reversible dominant-negative strategy regulate at cellular level within TME. Suppression via hypoxia-induced expression kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in...
<p>Differential gene expression and pathway analysis</p>
<p>Inhibition of autophagy promotes cell migration and fibronectin deposition</p>
<p>Differential gene expression and pathway analysis</p>
<p>Inhibition of autophagy promotes cell migration and fibronectin deposition</p>
<p>Schematic representation and immunoblot assessment of HRE-dnULK1</p>
<div>Abstract<p>Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored impact autophagy on pathophysiology breast using a novel hypoxia-dependent, reversible dominant-negative strategy regulate at cellular level within TME. Suppression via hypoxia-induced expression kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in...
<p>Immunohistochemical analysis of lung and liver metastasis</p>
<p>Supplementary materials, methods and figure legends</p>
<p>Schematic representation and immunoblot assessment of HRE-dnULK1</p>
<p>Supplementary materials, methods and figure legends</p>
<p>Immunohistochemical analysis of lung and liver metastasis</p>
<div>Abstract<p>Although neoadjuvant chemotherapy is a standard component of breast cancer treatment, recent evidence suggests that chemotherapeutic drugs can promote metastasis through poorly defined mechanisms. Here we utilize xenograft mouse models triple-negative to explore the importance chemotherapy-induced tumor-derived small extracellular vesicles (sEV) in metastasis. Doxorubicin (DXR) enhanced tumor cell sEV secretion accelerate pulmonary by priming premetastatic niche....