Shogo Kamikawaji
A5030867310- Lung Cancer Research Studies
- CAR-T cell therapy research
- Cancer therapeutics and mechanisms
- Immunotherapy and Immune Responses
- Parkinson's Disease Mechanisms and Treatments
- Plant Gene Expression Analysis
- Monoclonal and Polyclonal Antibodies Research
- Meta-analysis and systematic reviews
- NF-κB Signaling Pathways
- Plant biochemistry and biosynthesis
- Genetics, Bioinformatics, and Biomedical Research
- Signaling Pathways in Disease
- Fungal and yeast genetics research
- Nanoplatforms for cancer theranostics
The University of Tokyo
2009-2014
Parkinson's disease (PD) is a major adult-onset neurodegenerative disorder affecting the extrapyramidal motor system. A subset of patients develop PD as an autosomal dominant trait, which PARK8 caused by mutations in leucine-rich repeat kinase 2 (LRRK2) gene highlighted because its high frequency and clinicopathological similarity to sporadic PD. Previous studies have suggested that overactivation LRRK2 missense leads neuronal toxicity PARK8, although regulatory mechanism governs activity...
Abstract Small-cell lung cancer (SCLC) is an aggressive for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives ICI-resistant tumors, but not all patients with SCLC responsive. Herein, to integrate CD137 costimulatory function into a engager format and thereby augment efficacy, we generated CD3/CD137 dual-specific Fab engineered DLL3-targeted trispecific antibody (DLL3 trispecific). The was competitively...
Leucine-rich repeat kinase 2 (LRRK2) is extensively phosphorylated in cells within a region amino-terminal to the leucine-rich domain. Since phosphorylation this of LRRK2, including Ser910, Ser935, Ser955, and Ser973, significantly downregulated upon treatment with inhibitors it has been hypothesized that signaling pathways downstream activity LRRK2 are involved regulating although precise mechanism remained unknown. Here we examined effects on state at Ser955 series kinase-inactive mutants...
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified pedigrees of autosomal-dominant familial Parkinson's disease (PARK8). It has shown that activity LRRK2 is required for its neuronal toxicity, although how Parkinson mutations affect function not well characterized. In present study, we systematically characterized autophosphorylation by phosphopeptide mapping and Thr1348, Thr1349, Thr1357 as major sites. We found at downregulated Y1699C mutation, possibly through...
Abstract Background: Despite the approval of immune checkpoint inhibitors (ICIs), prognosis small cell lung cancer (SCLC) remains poor. DLL3 is upregulated in SCLC whereas expression normal tissues minimal, representing favorable profile as a therapeutic target. T engager (TCE) potent immunotherapy that redirects cells to tumors expressing specific antigen. Unlike ICIs, TCEs do not require recognition tumor antigens by and thus could be an alternative approach target where benefit ICIs...
<p>Supplementary Figure S2. Overview of the generation CD3/CD137 dual-specific Fab</p>
<div>Abstract<p>Small-cell lung cancer (SCLC) is an aggressive for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives ICI-resistant tumors, but not all patients with SCLC responsive. Herein, to integrate CD137 costimulatory function into a engager format and thereby augment efficacy, we generated CD3/CD137 dual-specific Fab engineered DLL3-targeted trispecific antibody (DLL3 trispecific). The...
<p>Supplementary Figure S4. DLL3 trispecific induces multiple cytokine production and DLL3- dependent cytotoxicity</p>
<p>Supplementary Figure S6. Cross-reactivity of DLL3 trispecific.</p>
<p>Supplementary Figure S9. The use of dexamethasone and tocilizumab does not limit the antitumor efficacy DLL3 trispecific.</p>
<p>Supplementary Figure S1. The composition of the antibodies</p>
<p>Supplementary Figure S8. DLL3 trispecific induced activation of tumor-infiltrating T cells.</p>
<p>Supplementary Figure S3. Binding of DLL3 trispecific to FcγRs, C1q, and FcRn. (</p>
<p>Supplementary Figure S7. DLL3 expression of SCLC xenograft models.</p>
<p>pharmacokinetic parameters of DLL3 trispecific in cynomolgus monkeys</p>
<p>Supplementary Figure S4. DLL3 trispecific induces multiple cytokine production and DLL3- dependent cytotoxicity</p>
<p>Supplementary Figure S8. DLL3 trispecific induced activation of tumor-infiltrating T cells.</p>
<p>Supplementary Figure S2. Overview of the generation CD3/CD137 dual-specific Fab</p>
<p>Supplementary Figure S6. Cross-reactivity of DLL3 trispecific.</p>
<p>Supplementary Methods</p>
<p>pharmacokinetic parameters of DLL3 trispecific in cynomolgus monkeys</p>
<p>Supplementary Figure S7. DLL3 expression of SCLC xenograft models.</p>
<p>Supplementary Figure S5. DLL3 trispecific induces cytotoxicity against non-SCLC tumors.</p>
<p>Supplementary Methods</p>