Yoko Kayukawa
A5085240991- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Cancer therapeutics and mechanisms
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Atherosclerosis and Cardiovascular Diseases
- Cancer, Hypoxia, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Chronic Lymphocytic Leukemia Research
- Cancer Cells and Metastasis
- Biosimilars and Bioanalytical Methods
- Acute Myeloid Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Wnt/β-catenin signaling in development and cancer
An anti–glypican 3/CD3 bispecific T cell–redirecting antibody (ERY974) is a promising therapeutic agent for solid tumors.
Current pharmacological treatments for endometriosis are limited to hormonal agents that can relieve pain but cannot cure the disease. Therefore, development of a disease-modifying drug is an unmet medical need. By studying human endometriotic samples, we found progression was associated with inflammation and fibrosis. In addition, IL-8 expression highly up-regulated in tissues closely correlated disease progression. We created long-acting recycling antibody against (AMY109) evaluated its...
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...
Abstract Background: TGF-β is a highly pleiotropic cytokine, consisting of three isoforms: TGF-β1, TGF-β2, and TGF-β3. The signaling known to be associated with poor response immune checkpoint inhibitors. Multiple agents targeting have been developed focus on the physiological effects in tumor microenvironment; however, inhibition multiple isoforms exhibited serious cardiac toxicity bleeding nonclinical studies. TGF-β1 expressed as inactive latent complex reported most among all tumors....
Abstract Identifying a strategy with strong efficacy against non-inflamed tumours is vital in cancer immune therapy. ERY974 humanized IgG4 bispecific T cell-redirecting antibody that recognizes glypican-3 and CD3. Here we examine the combination effect of chemotherapy (paclitaxel, cisplatin, capecitabine) treatment xenograft model. monotherapy shows minor antitumour on NCI-H446 xenografted tumours, as infiltration ERY974-redirected cells limited to tumour-stromal boundary. However, therapy...
Abstract Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non‐small‐cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and inflammatory (PI), squamous cell carcinoma (LUSQ) four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated landscape NSCLC tissues...
Resistance to immune checkpoint blockade remains challenging in patients with non-small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness immunotherapy. This study examined the landscape NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected tissues. Unsupervised clustering based on numbers percentages 30 types classified adenocarcinoma (LUAD) squamous carcinoma (LUSQ) into cold,...
Currently, ERY974, a humanized IgG4 bispecific T cell-redirecting antibody recognizing glypican-3 and CD3, is in phase I clinical trials. After first-in-human trial of an anti-CD28 agonist monoclonal resulting severe life-threatening adverse events, the minimal anticipated biological effect level approach has been considered for determining dose high-risk drugs. Accordingly, we aimed to determine ERY974 using both no observed approaches. In former, used 10% effective concentration value from...
Abstract Immune checkpoint inhibitors such as anti-PD1 antibodies have shown promising clinical responses in several solid tumors, however there remain patients who do not show an adequate response. Recent biomarker studies revealed that the presence of neoantigens tumor can determine level response, and thus next challenge will be how to target tumors with a neoantigen is too low recognized by endogenous cytotoxic T cells. Hope this area offered cell-redirecting antibody (TRAB), which...
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...
Abstract Introduction: Codrituzumab/GC33/RO5137382 (GC33) is a humanized monoclonal antibody that targets glypican-3 (GPC3), an oncofetal protein expressed on the cell surface of hepatocellular carcinoma (HCC). GC33 interacts with CD16/FcγR3 and triggers antibody-dependent cellular cytotoxicity. Because anti-PD-L1/PD-1 agents have shown marked antitumor effect in various cancer types including HCC, we investigated if plus anti-PD-L1 mAb combination can augment efficacy mouse hepatoma...
Abstract We present efficacy data for the T cell-redirecting antibody (TRAB) with highly potent anti-tumor efficacy. Anti-Glypican-3 (GPC3) TRAB is a humanized IgG4 bispecific that simultaneously binds to GPC3 on cancer cell surface and CD3 surface. Anti-GPC3 utilizes cells as effectors induce strong dependent cellular cytotoxicity (TDCC) in presence of GPC3-expressing cells. Treatment anti-GPC3 first activates by increasing expression CD25 CD69 also upregulating cytokines IL-2, IL-4, IL-6,...
<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>