- Immune Cell Function and Interaction
- Adenosine and Purinergic Signaling
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Adolescent and Pediatric Healthcare
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Multiple Myeloma Research and Treatments
- Macrophage Migration Inhibitory Factor
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Redox biology and oxidative stress
- Antibiotics Pharmacokinetics and Efficacy
- Analytical Methods in Pharmaceuticals
- Advanced Proteomics Techniques and Applications
- Analytical Chemistry and Chromatography
- Bipolar Disorder and Treatment
- Phagocytosis and Immune Regulation
- Viral gastroenteritis research and epidemiology
- Biosimilars and Bioanalytical Methods
- Microscopic Colitis
- Ferrocene Chemistry and Applications
- Immune cells in cancer
- HIV Research and Treatment
QIMR Berghofer Medical Research Institute
2019-2024
Tokyo Medical and Dental University
2016
Canadian Food Inspection Agency
2009
We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP-P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. demonstrate critical importance an eATP-P2X7-ASC-NALP3-inflammasome-IL18 pathway in antitumor activity mediated by enzyme blockade, rather than simply reducing adenosine as...
Multiple myeloma (MM), the second most common haematological malignancy, is a clonal plasma B-cell neoplasm that forms within bone marrow. Despite recent advancements in treatment, MM remains an incurable disease. Auranofin, linear gold(I) phosphine compound, has previously been shown to exert significant anti-myeloma activity by inhibiting thioredoxin reductase (TrxR) activity. A bis-chelated tetrahedral complex [Au(d2pype)2]Cl (where d2pype 1,2-bis(di-2-pyridylphosphino)ethane) was...
Immunotherapy holds promise for patients with multiple myeloma (MM), but little is known about how MM-induced immunosuppression influences response to therapy. Here, we investigated the impact of disease progression on immunotherapy efficacy in Vk*MYC mouse model. Treatment agonistic anti-CD137 (4-1BB) mAbs efficiently protected mice when administered early failed contain MM growth delayed more than 3 weeks after tumor cell challenge. The quality CD8+ T CD137 stimulation was not altered by...
Mass spectrometry-based proteomics revolutionized global proteomic profiling. Although high molecular weight abundant proteins are readily sampled in studies, less low often underrepresented. This includes biologically important classes of including ligands, growth factors, peptide hormones and cytokines. extensive fractionation can facilitate achieving better coverage proteome, it requires additional infrastructure, mass spectrometry time labour. There is need for a simple method that...
T-cell-engaging bispecific antibody (T-BsAb, also known as BiTE) therapy has emerged a powerful therapeutic modality against multiple myeloma. Given that T-BsAb redirects endogenous T cells to eliminate tumor cells, reinvigorating dysfunctional may be potential approach improve the efficacy of T-BsAb. While various immunostimulatory cytokines can potentiate effector T-cell functions, optimal cytokine treatment for is yet established, partly due concern release syndrome driven by aberrant...
An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of fluoroquinolones–ciprofloxacin (CIPRO), danofloxacin (DANO), enrofloxacin (ENRO) and sarafloxacin (SARA)–in aquaculture products, specifically salmon, shrimp tilapia. After initial sample extraction with an acidic acetonitrile solution, extract diluted dichloromethane centrifuged, then aliquot concentrated applied to a C18 solid-phase cartridge second time. The...
T-cell-engaging bispecific antibodies (T-BsAb) have produced impressive clinical responses in patients with relapsed/refractory B-cell malignancies, although treatment failure remains a major challenge. Growing evidence suggests that complex interplay between immune cells and tumor is implicated the mechanism of action therefore, understanding regulatory mechanisms might provide clue for how to improve efficacy T-BsAb therapy. Here, we investigated functional impact T (Treg) on anti-tumor...
Abstract CD3-engaging bispecific antibodies (BsAbs) have emerged as powerful therapeutic approaches by their ability to redirect T cells eliminate tumor in a major histocompatibility complex–independent manner. However, how we can potentiate the efficacy of BsAbs remains largely unknown. To address this question, investigated immunological mechanisms action BsAb cotargeting CD3 and B-cell maturation antigen (BCMA) syngeneic preclinical myeloma models. Treatment with CD3/BCMA stimulated...
The upregulation of inhibitory molecules is a major driver immune escape in cancer. In contrast, less known about the regulation T cell activating receptors within tumor microenvironment. Here, we describe that derived CD155, transmembrane glycoprotein immunoglobulin superfamily, downregulates receptor CD226 (DNAM-1) mouse and human CD8+ cells, leading to profound loss effector function cancer evasion. Mechanistically, CD155 drives internalisation through phosphorylation tyrosine 319...
<div>Abstract<p>We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP–P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. We demonstrate critical importance an eATP–P2X7–ASC–NALP3-inflammasome–IL18 pathway in antitumor activity mediated by enzyme blockade, rather than...
<p>Supplementary Methods, Figures, Legends and Tables</p>
<p>Supplementary Methods, Figures, Legends and Tables</p>
<div>Abstract<p>We explored the mechanism of action CD39 antibodies that inhibit ectoenzyme conversion extracellular ATP (eATP) to AMP and thus potentially augment eATP–P2-mediated proinflammatory responses. Using syngeneic humanized tumor models, we contrast potency anti-CD39 mAbs with other agents targeting adenosinergic pathway. We demonstrate critical importance an eATP–P2X7–ASC–NALP3-inflammasome–IL18 pathway in antitumor activity mediated by enzyme blockade, rather than...