A5049472344- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Antifungal resistance and susceptibility
- Cancer Immunotherapy and Biomarkers
- Gut microbiota and health
- T-cell and B-cell Immunology
- Probiotics and Fermented Foods
- Fungal Infections and Studies
- 3D Printing in Biomedical Research
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- Immune responses and vaccinations
- Advancements in Semiconductor Devices and Circuit Design
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Cutaneous lymphoproliferative disorders research
- Lymphoma Diagnosis and Treatment
- Reproductive System and Pregnancy
- Immunodeficiency and Autoimmune Disorders
- Pancreatic and Hepatic Oncology Research
- Nematode management and characterization studies
- Protist diversity and phylogeny
Tessa Therapeutic (Singapore)
2024
Singapore Immunology Network
2015-2021
Agency for Science, Technology and Research
2015-2021
The human fetal immune system begins to develop early during gestation; however, factors responsible for immune-priming remain elusive. We explored potential exposure microbial agents in utero and their contribution toward activation of memory T cells tissues. profiled microbes across organs using 16S rRNA gene sequencing detected low but consistent signal gut, skin, placenta, lungs the 2nd trimester gestation. identified several live bacterial strains including Staphylococcus Lactobacillus...
Gut microbes live in symbiosis with their hosts, but how mutualistic animal-microbe interactions emerge is not understood. By adaptively evolving the opportunistic fungal pathogen Candida albicans mouse gastrointestinal tract, we selected strains that only had lost main virulence program also protected new hosts against a variety of systemic infections. This protection was independent adaptive immunity, arose as early single day postpriming, dependent on increased innate cytokine responses,...
Abstract Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and fungal adapting antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential confer multiple phenotypes same cells. Here, we analyzed mechanisms by which Candida albicans, most prevalent human pathogen, acquires ability survive Strikingly, adaptation types of drugs was accompanied acquisition specific whole-chromosome aneuploidies, with some aneuploid karyotypes...
Abstract Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored biochemical mechanisms that drive pro-tumor macrophage functions; however role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with and macrophages study how IF affects migration its potential contribution The presence either or individually increased directedness speed....
Candida albicans is responsible for ~400,000 systemic fungal infections annually, with an associated mortality rate of 46-75%. The human gastrointestinal (GI) tract represents the largest natural reservoir species and a major source infections. However, factors that control GI colonization by are not completely understood. We hypothesized cell wall would play important role in determining competitive fitness mammalian tract. To test this hypothesis, we generated systematic collection...
Candida albicans is the most important fungal pathogen of humans, causing severe infections, especially in nosocomial and immunocompromised settings. However, it also prevalent fungus normal human microbiome, where shares its habitat with hundreds trillions other microbial cells. Despite weak organic acids (WOAs) being among abundant metabolites produced by bacterial microbiota, little known about their effect on C. albicans. Here we used a sequencing-based profiling strategy to...
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,...
ABSTRACT Candida albicans is the leading cause of fungal infections; but it also a member human microbiome, an ecosystem thousands microbial species potentially influencing outcome host-fungal interactions. Accordingly, antibacterial therapy raises risk candidiasis, yet underlying mechanism currently not fully understood. We hypothesize existence bacterial metabolites that normally control C. growth and resistance mechanisms against these metabolites. Among most abundant microbiota-derived...
Candida albicans is a ubiquitous fungal symbiont that resides on diverse human barrier surfaces. Both mammalian and cells can convert arachidonic acid into the lipid mediator, prostaglandin E2 (PGE2), but physiological significance of fungus-derived PGE2 remains elusive. Here we report C. mutant deficient in production suffered loss competitive fitness murine gastrointestinal (GI) tract supplementation mitigated this defect. Impaired affected neither vitro nor hyphal morphogenesis virulence...
Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. outcompetes local microbiota during candidiasis episodes. Under normal conditions, members gastrointestinal (GI) were shown to keep colonization under control. By releasing weak organic acids (WOAs), bacteria are able moderate yeast growth. This mechanism displays synergistic effect vitro with absence glucose medium culture, which underlines complex interactions...
Serial passaging of the human fungal pathogen Candida albicans in gastrointestinal tract antibiotics-treated mice selects for virulence-attenuated strains. These gut-evolved strains protect host from infection by a wide range pathogens via trained immunity. Here, we further investigated molecular and cellular mechanisms underlying this innate immune memory. Both Dectin-1 (the main receptor β-glucan; well-described training molecule cell wall) Nod2 (a described to mediate BCG-induced...
Abstract Allogeneic chimeric antigen receptor (CAR)–expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination recipient immune cells. Moreover, just as with allogeneic CAR susceptible to activation-induced cell death (AICD) caused chronic exposure (CAE). Granzyme B– Fas/Fas ligand–initiated caspase-mediated apoptoses key mechanisms of T-cell T/NK cell–mediated allorejection or CAE. We explored a...
<p>Supplementary Figure S1. Gating strategies employed in the study. Sample gating strategy for <i>in vitro</i> MLR assay using PBMCs as “recipient” cells (A) or Allo-T ‘recipient’ (B). C, expression of intracellular surface markers on T cells. D, to determine apoptotic with annexin V and live/dead staining. E, “donor” human harvested from animal blood. Fig. 1 associated supplementary figures A B (without target cells). 2D used C. All gates were drawn based...
<p>Supplementary Figure S11. Overexpression of SB9(CAS) in activated CD30.CAR with 4-1BB spacer (CD30.bb) TCRαβKO ATCs and CD19.CAR protects them from allogeneic rejection enhances anti-tumor efficacy in-vitro as described 3A. A, Flow cytometry analysis NALM6 cells modified to overexpress truncated CD30 were gene-edited for the knockout HLA class I II (HLADKO NALM6-CD30). HLADKO NALM6-CD30 purified either by FACS or clonal selection. B C, Representative ‘donor’ CD30.bb ATC (B) (C)...
<p>Supplementary Figure S10. Overexpression of SB9(CAS) on CD19.CAR TCRαβKO ATCs reduces the amount caspase 8 active p18 fragment produced. A and C, SDS-PAGE analysis expression in ATCs, where is located at 18 kDa. The corresponding calnexin same membrane also shown 90 B D, Densitometry normalized to control as loading control, each time point.</p>
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR)–expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination recipient immune cells. Moreover, just as with allogeneic CAR susceptible to activation-induced cell death (AICD) caused chronic exposure (CAE). Granzyme B– Fas/Fas ligand–initiated caspase-mediated apoptoses key mechanisms of T-cell T/NK cell–mediated allorejection or CAE. We...
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR)–expressing T cells offer many advantages over autologous therapies, but their benefits are curtailed by graft-versus-host disease and elimination recipient immune cells. Moreover, just as with allogeneic CAR susceptible to activation-induced cell death (AICD) caused chronic exposure (CAE). Granzyme B– Fas/Fas ligand–initiated caspase-mediated apoptoses key mechanisms of T-cell T/NK cell–mediated allorejection or CAE. We...
<p>Supplementary Figure S14. Overexpression of SB9(CAS) in ‘donor’ CD30.CAR with 4-1BB spacer (CD30.bb) EBVSTs increases resistance to allorejection a B-ALL model which CAR T cell and ‘recipient’ levels were quantified via IVIS imaging flow cytometry, respectively. A, Manufacturing timeline for the generation CD30.bb expressing eGFP-ffLuc. B, Schematic in-vivo (C-D), where 2.5 x 106 HLADKO NALM6-CD30 tumor cells injected intravenously into NSG (MHCKO) mice. 18 days later, 5...
<p>Supplementary Figure S15. Allogeneic rejection of ‘donor’ CD30.CAR with 4-1BB spacer (CD30.bb) EBVSTs occurs in mice engrafted HLA-mismatched ‘recipient’ PBMCs a cutaneous T cell lymphoma (CTCL) allorejection model. A, CD30, HLA-ABC and HLA-DRDPDQ expression on wildtype (WT) compared to human leukocyte antigen (HLA) class I II knockout HuT 78 tumor cells by Crispr-Cas9 gene editing. B, Quantified bioluminescent signals GFP-ffluc-expressing CD30.bb at the sites presence (black line)...
<p>Supplementary Figure S5. Cytokine secretion profiles of CD30.CAR with 4-1BB spacer (CD30.bb) EBVSTs expressing different forms SB9, in monoculture or after co-culture KM-H2 tumor cells. A, Schematic <i>in vitro</i> cytokine assay where effector CD30.bb were either untreated and cultured co-cultured cells at a 1:1 ratio, the absence exogenous cytokines. B, concentration measured from supernatant collected 24 h co-culture.</p>
<p>Supplementary Figure S17. CD30-positive B-cell acute lymphoblastic leukemia (B-ALL) burden of two in-vivo models that were being used to test SB9-mediated protection ‘donor’ cells against allorejection (allorejection model) and AICD (AICD model), respectively. Bioluminescence signals from HLADKO NALM6-CD30.eGFP-ffLuc prepared either FACS or clonal selection measured at baseline (day 0). Each point represents an individual mouse. The lines with error bars indicate mean + SD.</p>
<p>Supplementary Figure S7. Manufacturing of Allo-T cells which are pre-primed alloreactive ‘recipient’ that recognize and kill ‘donor’ cells. A, timeline for the generation Allo-T. B, CD30 expression CD30KO determined by staining with two different antibody clones, BY88 BerH8, flow cytometry analysis.</p>
<p>Supplementary Figure S4. CD30.CAR with 4-1BB spacer (CD30.bb) EBVSTs expressing different forms of SB9 had similar CD30.bb expression and T cell characteristics. (A, left) SDS-PAGE analysis from a representative donor, where the top band (∼62 kDa) indicates pre-formed GzmB complexes in cytosol bottom (∼43 functional monomer. Transduction was carried out presence IL-7 (10 ng/mL) either low or high (100 IL-15 concentration, as denoted by ‘L’ ‘H’ respectively. right) Densitometry...
<p>Supplementary Figure S12. Allogeneic rejection of ‘donor’ CD30.CAR with 4-1BB spacer (CD30.bb) EBVSTs occurs the administration alloreactive ‘recipient’ Allo-T cells in a CD30-positive B-cell acute lymphoblastic leukemia (B-ALL) mouse model. A, Schematic in-vivo B-ALL allorejection model for (B-D), which 2.5 x 106 HLADKO NALM6-CD30.eGFP-ffLuc, FACS selected truncated CD30 (tCD30) overexpression and HLA I II knockout (HLADKO), were injected intravenously into NSG (MHCKO) mice. 15...