A5001774669- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Hepatitis B Virus Studies
- Cancer Cells and Metastasis
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Mathematical Biology Tumor Growth
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Virus-based gene therapy research
- Renal Transplantation Outcomes and Treatments
- RNA and protein synthesis mechanisms
- Radiopharmaceutical Chemistry and Applications
- Hepatitis Viruses Studies and Epidemiology
- Anesthesia and Sedative Agents
- Cancer, Hypoxia, and Metabolism
- Animal Virus Infections Studies
- Neuroblastoma Research and Treatments
- Innovative Microfluidic and Catalytic Techniques Innovation
Agency for Science, Technology and Research
2018-2025
Institute of Molecular and Cell Biology
2018-2025
Duke-NUS Medical School
2020
Singapore Institute for Clinical Sciences
2017-2018
Tokyo Medical and Dental University
2015
Queen Mary University of London
2015
The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, discontinuation associated with and biochemical relapse and, consequently, the majority life-long.
Abstract Glioblastoma (GBM) is the most common primary malignant brain cancer in adults with a dismal prognosis. Temozolomide (TMZ) first‐in‐line chemotherapeutic; however, resistance frequent and multifactorial. While many molecular genetic factors have been linked to TMZ resistance, role of solid tumor morphology microenvironment, particularly blood‐brain barrier (BBB), unknown. Here, authors investigate these using complex vitro model for GBM its surrounding BBB. The recapitulates...
The extent of and the oncogenic role played by alternative splicing (AS) in cancer are well documented. Nonetheless, only few studies have attempted to dissect individual gene function at an isoform level. Here, we focus on AS factors during prostate progression, as these known undergo extensive potential affect hundreds downstream genes. We identified exon 7 (ex7) MBNL1 (Muscleblind-like 1) transcript being most differentially included cancer, both cell lines patients' samples. In contrast,...
Background and Aims HBV‐specific T‐cell receptor (HBV‐TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is molecularly engineer TCR‐T that could retain polyfunctionality in such patients while minimizing associated risk of organ Approach Results We first analyzed how drugs interfere with vivo function transplanted HBV‐HCC...
Abstract Engineered T cells transiently expressing tumor-targeting receptors are an attractive form of engineered cell therapy as they carry no risk insertional mutagenesis or long-term adverse side-effects. However, multiple rounds treatment often required, increasing patient discomfort and cost. To mitigate this, we sought to improve the antitumor activity transient by screening a panel small molecules targeting epigenetic regulators for their effect on cytotoxicity. Using model targetting...
The desmoplastic nature of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) prevents infiltration T cells and penetration chemotherapeutic drugs, posing a challenge to validation targeted therapies, including cell immunotherapies. We present an in vitro 3D PDAC-TME model observe quantify across vasculature. In three-channel microfluidic device, PDAC are cultured collagen matrix central channel surrounded, on one side, by endothelial (ECs) mimic blood vessel and,...
Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific viral tumor antigens overcome exhaustion by down-modulating co-inhibitory receptor PD-1. developed a novel lentiviral transduction protocol achieve preferential targeting endogenous or TCR-redirected, antigen-specific CD8 shRNA...
Emerging base editing technology exploits CRISPR RNA-guided DNA modification effects for highly specific C > T conversion, which has been used to efficiently disrupt gene expression. These tools can enhance synthetic cell immunity by restricting specificity, addressing histocompatibility leukocyte antigen (HLA) barriers, and promoting persistence. We report lentiviral delivery of a hepatitis B-virus (HBV)-specific recombinant receptor (rTCR) linked single-guide RNA simultaneous disruption...
Summary Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated the immunosuppressants required to prevent graft rejection. To circumvent effects immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T (IDRA HBV-TCR). However, their ability eliminate HBV-HCC in whole blood has never been tested, whether lytic efficacy...
Abstract Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with a dismal prognosis of 15 months. This despite decades research and improvements surgery radiotherapy. Temozolomide (TMZ) only first-in-line chemotherapeutic; however, resistance frequent multifactorial. While many molecular genetic factors have been linked to TMZ resistance, role solid tumor morphology microenvironment (TME), particularly blood-brain barrier (BBB), unknown. Complex 3D vitro models...
Abstract Development of efficacious therapeutic strategies against solid tumors is limited by the lack pre-clinical models that can reliably predict treatment outcomes in patients. This primarily because often do not accurately reflect complexity tumor microenvironment (TME). The TME consists vasculature, stromal cells and immune promote resistance or prevent targeted drug cell therapy. Here, we developed an vitro vascularized liver model a microfluidic device to evaluate delivery...
e14648 Background: Osteoclastic giant cell tumor of the pancreas (OGCTP) is a rare subtype pancreatic cancer. It has been variably described in case reports as cancer with pleomorphic, anaplastic, spindle cell, undifferentiated or mixed histology. Clinical and pathologic data regarding this are very limited. Methods: We conducted retrospective review patient records above histologies at single institution from 1994 to 2008. Archival pathology specimens were independently reviewed by two...
Abstract Engineered T cells transiently expressing tumor-targeting receptors are an attractive form of engineered cell therapy as they carry no risk insertional mutagenesis or long-term adverse side-effects. However, multiple rounds treatment often required, increasing patient discomfort and cost. To mitigate this, we sought to improve the antitumor activity transient by screening a panel small molecules targeting epigenetic regulators for their effect on cytotoxicity. Using model targetting...
Abstract Adoptive cell transfer (ACT) has been highly efficient in targeting certain refractory cancers and remains potentially effective for other as new targets of cancer-immune interactions are revealed. ACT involves isolating immunocompetent cells from cancer patients, expanding them ex vivo, infusing back into the patient. Cells used often effector cells, typically T isolated patient’s peripheral blood then engineered to target by incorporating a receptor (TCR) or chimeric antigen...
Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with a dismal prognosis. Currently, Temozolomide (TMZ) and Bevacizumab are main approved agents for recurrent GBM, respectively. However, TMZ resistance frequent does not improve overall survival. The heterogeneity of GBM presence highly selectively permeable blood-brain barrier (BBB) preclude use chemotherapeutics other malignancies. Meanwhile, new therapy development limited part because pre-clinical...
Microfluidic Models In article number 2302280, Andrea Pavesi and co-workers develop an in vitro 3D glioblastoma model, that incorporates a perfusable blood-brain barrier. The model recapitulates key features of clinical disease, such as diffusive infiltrating tumor front tumor-associated dysregulation vascular permeability. authors further demonstrate the compatibility with next-generation ultra-sensitive mass spectrometry to explore proteins involved tumorigenesis drug resistance.
Abstract Solid tumors present particular obstacles for cell therapies, which need to be reflected in pre-clinical models effective therapy validation. For example, tumor biology varies along with the mass, and microenvironment (TME), consisting of vasculature, stromal cells immune cells, can become corrupted promote resistance or prevent targeting efficacy. We developed an vitro vascularized human solid model recapitulates these key features TME a microfluidic device, allowing more reliable...