A5020196665- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Innovation and Socioeconomic Development
- Cell Adhesion Molecules Research
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- Nanoparticle-Based Drug Delivery
- Cardiac Fibrosis and Remodeling
- Toxin Mechanisms and Immunotoxins
- Chromosomal and Genetic Variations
- Chemokine receptors and signaling
- Adrenal and Paraganglionic Tumors
- Immune cells in cancer
- RNA regulation and disease
- Protease and Inhibitor Mechanisms
University of Pennsylvania
2013-2019
Stanford University
2017-2019
Cancer Research Institute
2013
Thomas Jefferson University
2013
Institute of Molecular Biology, Academia Sinica
2013
The Wistar Institute
2013
Academia Sinica
2013
Cancer Research Institute of the Slovak Academy of Sciences
2013
Institute of Cellular and Organismic Biology, Academia Sinica
2008-2009
National Taiwan University
2008
The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T may offer several advantages. We developed a retroviral construct specific for mouse fibroblast activation protein (FAP), comprising single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with CD8α hinge and transmembrane regions, human CD3ζ 4-1BB domains. transduced muFAP-CAR secreted IFN-γ killed...
Abstract Chimeric antigen receptor (CAR)–modified adoptive T-cell therapy has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is immune-suppressive effects induced both naturally occurring and genetically modified tumor-infiltrating lymphocytes (TIL) by inhibitory receptors (IR), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR activity against To address this possibility,...
Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal (CASC) are heterogeneous population that provides both negative positive signals for cell growth metastasis. Fibroblast activation protein (FAP) is marker major subset CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent prognostic factor multiple types human malignancies. Prior studies established depletion FAP(+) inhibits by...
Tracking nucleic acids in living cells Fluorescence situ hybridization (FISH) is a powerful molecular technique for detecting cells. However, it requires cell fixation and denaturation. Wang et al. found that CRISPR-Cas9 protects guide RNAs from degradation only when bound to target DNA. Taking advantage of this target-dependent stability switch, they developed labeling technique, named CRISPR LiveFISH, detect DNA RNA using fluorophore-conjugated with Cas9 Cas13, respectively. LiveFISH...
Antitumor treatments based on the infusion of T cells expressing chimeric antigen receptors (CAR cells) are still relatively ineffective for solid tumors, due to presence immunosuppressive mediators [such as prostaglandin E2 (PGE2) and adenosine] poor T-cell trafficking. PGE2 adenosine activate protein kinase A (PKA), which then inhibits receptor (TCR) activation. This inhibition process requires PKA localize immune synapse via binding membrane ezrin. We generated CAR that expressed a small...
Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. Novel treatment strategies derived from increased knowledge molecular oncology are constantly being developed to cure this disease. Here, we used phage display identify a novel peptide (SP94), which binds specifically hepatocellular cells. In vitro, clone PC94 was shown bind cell lines by ELISA and flow cytometry analysis. vivo, homed tumor tissues but not normal visceral organs in severe combined immunodeficient...
T cell trafficking into tumors depends on a "match" between chemokine receptors effector cells (e.g., CXCR3 and CCR5) tumor-secreted chemokines. There is often chemokine/chemokine receptor "mismatch", with producing minute amounts of chemokines, resulting in inefficient targeting effectors to tumors. We aimed alter produce higher levels CXCL11, ligand, attract more following immunotherapy. Mice bearing established subcutaneous were studied. In our first approach, we used modified chimeric...
Pancreatic ductal adenocarcinomas (PDAs) are desmoplastic and can undergo epithelial-to-mesenchymal transition to confer metastasis chemoresistance. Studies have demonstrated that phenotypically functionally distinct stromal cell populations exist in PDAs. Fibroblast activation protein-expressing (FAP-expressing) cells act enhance PDA progression, while α-smooth muscle actin myofibroblasts restrain PDA. Thus, identification of precise molecular targets mediate the protumorigenic activity...
Tumor-infiltrating lymphocytes (TILs) become hypofunctional, although the mechanisms are not clear. Our goal was to generate a model of human tumor-induced TIL hypofunction study and test anti-human therapeutics.We transduced T cells with published, optimized T-cell receptor (TCR) that is directed peptide within cancer testis antigen, NY-ESO-1. After demonstrating antigen-specific in vitro activity, these were used target lung line expressed NY-ESO-1 appropriate HLA context growing...
Abstract Chimeric antigen receptors (CAR) bearing an antigen-binding domain linked in cis to the cytoplasmic domains of CD3ζ and costimulatory have provided a potent method for engineering T-cell cytotoxicity toward B-cell leukemia lymphoma. However, resistance immunotherapy due loss effector function remains significant barrier, especially solid malignancies. We describe alternative chimeric immunoreceptor design which we fused single-chain variable fragment recognition transmembrane...
Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen tumor microenvironment plays a crucial role regulating progression. We have shown that type III collagen (Col3), component stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During course these wound-healing studies, we noted tumors developed at higher frequency Col3(+/-) mice compared to wild-type littermate controls. We, therefore, examined effect Col3...
It is known that solid tumors recruit new blood vessels to support tumor growth, but the molecular diversity of receptors in angiogenic might also be used clinically develop better targeted therapy. In vivo phage display was identify peptides specifically target vessels. Several novel were identified as being able recognize vasculature not normal severe combined immunodeficiency (SCID) mice bearing human tumors. These tumor-homing bound surgical specimens various cancers. The peptide-linked...
Targeted delivery of drugs to tumors represents a significant advance in cancer diagnosis and therapy. Therefore, development novel tumor-specific ligands or pharmaceutical nanocarriers is highly desirable. In this study, we utilized phage display identify new targeting peptide, SP90, which specifically binds breast cells, recognizes tumor tissues from patients. We used confocal electron microscopy reveal that conjugation SP90 with liposomes enables efficient into cells through endocytosis....
The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, epigenetic modifiers enable sequence-specific regulation gene expression chromatin state. These CRISPR-Cas-based technologies have contributed to...
Background Primary hyperaldosteronism ( PHA ) in cats occurs as a consequence of excessive hormone production by an adrenocortical tumor. Median survival time, association between tumor type and prognosis, the likelihood that require continued medical therapy after surgery have not been systematically evaluated. Objectives To determine median time with treated unilateral adrenalectomy. examine if type, anesthesia or location (left right side) affect affected postoperative treatment for...
IL ‐15 is an essential survival factor for CD 8αα + intestinal intraepithelial lymphocytes (i IEL s) in vitro and vivo. However, the ‐15‐induced signals primary i s remains elusive. Although B cl‐2 level positively correlates with R α expression epithelial cells, overexpression of only moderately restores γδ Il15 −/− mice. Here, we found that promptly activated a J ak3‐ ak1‐ PI 3 K ‐ A kt pathway led to upregulation M cl‐1. This also induced delayed but sustained ERK 1/2 activation, which...
Abstract Visualizing the real-time dynamics of genome rearrangement in single living cells is core to studying genomics and diagnostics. Here, we report a robust, versatile approach named CRISPR Live -cell fluorescent s itu h ybridization (LiveFISH) for multi-locus tracking cytogenetic detection broad variety cell types including primary cells. LiveFISH utilizes an intrinsic stability switch guide RNAs, which enables efficient accurate chromosomal disorders such as Patau Syndrome prenatal...
Abstract Infusion of T cells expressing chimeric antigen receptors (CAR cells) is still relatively ineffective in solid tumors due to the presence immunosuppressive mediators (such as prostaglandin E2 (PGE2) and adenosine), poor cell trafficking. Since PGE2 adenosine activate protein kinase A (PKA), which then inhibits receptor (TCR) activation, we generated CAR that expressed a small peptide called “regulatory subunit I anchoring disruptor” (RIAD) association (PKA) with ezrin; this...