A5053208128- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
- Macrophage Migration Inhibitory Factor
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- Crystallization and Solubility Studies
- NF-κB Signaling Pathways
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Animal Virus Infections Studies
- X-ray Diffraction in Crystallography
- bioluminescence and chemiluminescence research
- RNA Interference and Gene Delivery
Erasmus MC
2023-2025
The University of Tokyo
2021-2024
Tokyo University of Science
2020-2023
National Institute of Biomedical Innovation, Health and Nutrition
2020-2022
Osaka University
2020
5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a mouse-selective stimulator of interferon gene (STING) agonist exerting STING-dependent anti-tumor activity. Although DMXAA cannot fully activate human STING, reached phase III in lung cancer clinical trials. How effective against completely unknown. Here, we show that partial STING interfering with agonistic activation, which may explain its effect observed humans, as was reported to be pro-tumorigenic for cells low antigenicity. Furthermore,...
Abstract Agonists for TLR9 and stimulator of IFN genes (STING) offer therapeutic applications as both anti-tumor agents vaccine adjuvants, though their clinical are limited; the clinically available agonist is a weak inducer STING agonists induce undesired type 2 immunity. Yet, combining overcame these limitations by synergistically inducing innate adaptive IFNγ to become an advantageous 1 adjuvant, suppressing immunity, in addition exerting robust activities when used monotherapeutic agent...
Abstract Cytotoxic T cell (CTL) exhaustion is driven by chronic receptor (TCR) stimulation, leading to a dysfunctional state of cells. Exhausted CTLs exhibit diminished effector function against infections and cancers. Therefore, reducing CTL may re-establish effective adaptive immune responses. One feature exhausted the sustained stable expression transcription factor thymocyte selection-associated high mobility group box (TOX). Downregulating TOX in CD8+ cells enhances their antitumor...
Immune checkpoint blockade (ICB) immunotherapies have emerged as promising strategies for the treatment of cancer; however, there remains a need to improve their efficacy. Determinants ICB efficacy are frequency tumor mutations, associated neoantigens, and T cell response against them. Therefore, it is expected that neoantigen vaccinations boost antitumor would therapy The aim this study was develop highly immunogenic vaccine using pattern recognition receptor agonists in combination with...
In 2020, two mRNA-based vaccines, encoding the full length of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, have been introduced for control disease (COVID-19) pandemic 1,2 . However, reactogenicity, such as fever, caused by innate immune responses to vaccine formulation remains be improved. Here, we optimized a lipid nanoparticle (LNP)-based mRNA candidate, SARS-CoV-2 protein receptor-binding domain (LNP-mRNA-RBD), which showed improved immunogenicity removing...
Abstract Immune potentiators, termed adjuvants, trigger early innate immune responses to ensure the generation of robust and long‐lasting adaptive vaccines. Presented here is a study that takes advantage self‐assembling small‐molecule library for development novel vaccine adjuvant. Cell‐based screening subsequent structural optimization led discovery simple, chemically tractable deoxycholate derivative (molecule 6 , also named cholicamide) whose well‐defined nanoassembly potently elicits in...
Adjuvants are important vaccine components, composed of a variety chemical and biological materials that enhance the antigen-specific immune responses by stimulating innate cells in both direct indirect manners to produce cytokines, chemokines, growth factors. It has been developed empirical methods for decades considered difficult choose single screening method an ideal adjuvant, due their diverse biochemical characteristics, complex mechanisms of, species specificity adjuvanticity. We...
Protein or peptide cancer vaccines usually include immune potentiators, so-called adjuvants. However, it remains challenging to identify structurally simple, chemically accessible synthetic molecules that are effective and safe as vaccine adjuvant. Here, we present cholicamideβ (6), a self-assembling small-molecule adjuvant with an improved toxicity profile proven efficacy in vivo. We demonstrate which is less cytotoxic than its parent compound, forms virus-like particles potently activate...
Abstract Immunotherapies such as immune checkpoint blockade (ICB) therapies have been developed in the last years a promising strategy for treatment of cancer, however there remains need to improve their efficacy. The most critical factor that affects efficacy ICB therapies, is frequency tumor mutations, associated neoantigens generated and T-cell response against them. Therefore, it expected neoantigen vaccinations would therapy by boosting neoantigen-specific T cell response. aim this...
Abstract 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a mouse-selective stimulator of interferon gene (STING) agonist exerting STING-dependent anti-tumor activity. Although DMXAA can not fully activate human STING, reached phase III in lung cancer clinical trials. How effective against completely unknown. Here, we show that partial STING interfering with agonistic activation, which may explain its effect observed humans, as was reported to be pro-tumorigenic for cells low antigenicity....
Abstract Immune potentiators, termed adjuvants, trigger early innate immune responses to ensure the generation of robust and long‐lasting adaptive vaccines. Presented here is a study that takes advantage self‐assembling small‐molecule library for development novel vaccine adjuvant. Cell‐based screening subsequent structural optimization led discovery simple, chemically tractable deoxycholate derivative (molecule 6 , also named cholicamide) whose well‐defined nanoassembly potently elicits in...