A5014080480- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Pharmacogenetics and Drug Metabolism
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Bladder and Urothelial Cancer Treatments
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- T-cell and B-cell Immunology
- Estrogen and related hormone effects
- Genetic factors in colorectal cancer
- vaccines and immunoinformatics approaches
- Renal cell carcinoma treatment
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Cancer-related gene regulation
- Inflammatory mediators and NSAID effects
- Lymphoma Diagnosis and Treatment
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Ferroptosis and cancer prognosis
- Renal and related cancers
- Colorectal Cancer Surgical Treatments
National Institute of Biomedical Innovation, Health and Nutrition
2023-2025
Japanese Foundation For Cancer Research
2017-2024
ImmunoGen (United States)
2024
University of Chicago
2014-2023
The Cancer Institute Hospital
2019-2023
Tokushima University
2011-2019
National Cancer Centre Japan
2019
Mayo Clinic
2019
The University of Texas MD Anderson Cancer Center
2019
University of Chicago Medical Center
2014-2016
Abstract The coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly expanded to a global pandemic. However, numbers of infected cases, deaths, and mortality rates related COVID-19 vary from country country. Although many studies were conducted, the reasons these differences have not been clarified. In this study, we comprehensively investigated 12,343 SARS-CoV-2 genome sequences isolated patients/individuals in six geographic areas identified total 1234 mutations...
Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify molecular mechanisms involved in carcinogenesis TNBC and identify target molecules for novel anticancer drugs, we analyzed gene expression profiles 30 TNBCs as well 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 321 transcripts significantly upregulated downregulated TNBC, respectively. In particular, profile...
Immune checkpoint blockade against programmed cell death 1 (PD-1) and its ligand PD-L1 often induces durable tumor responses in various cancers, including non–small lung cancer (NSCLC). However, therapeutic resistance is increasingly observed, the mechanisms underlying anti–PD-L1 (aPD-L1) antibody treatment have not been clarified yet. Here, we identified two unique secreted splicing variants, which lacked transmembrane domain, from aPD-L1–resistant NSCLC patients. These variants worked as...
An 80‐year‐old man, who developed multiple lymph node and skin metastasis of malignant melanoma, received nivolumab monotherapy. Two weeks after the first dose, he experienced anorexia fatigue, suffered from progressive, severe dyspnea muscle weakness. We diagnosed him with myocarditis, myositis, myasthenic crisis induced by nivolumab. commenced steroid therapy, immune absorption plasma exchange i.v. immunoglobulin succeeded in saving his life. Because serum level anti‐acetylcholine receptor...
Abstract To control and prevent the current COVID-19 pandemic, development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell B-cell responses know how our immune system responding this deleterious virus. However, little information currently available about target epitopes coronavirus (SARS-CoV-2) induce host responses. Through a comprehensive bioinformatic screening potential derived from SARS-CoV-2 sequences for HLAs commonly...
Purpose The clinical efficacy of tamoxifen is suspected to be influenced by the activity drug-metabolizing enzymes and transporters involved in formation, metabolism, elimination its active forms. We investigated relationships polymorphisms transporter genes CYP2D6 outcome patients receiving tamoxifen. Patients Methods studied 282 with hormone receptor–positive, invasive breast cancer monotherapy, including 67 who have been previously reported. effects allelic variants haplotype-tagging...
The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized CYP2D6 to its active forms antiestrogenic metabolite, 4‐hydroxytamoxifen and endoxifen. We investigated predictive value * 10 allele, which decreased activity, for that received adjuvant monotherapy after surgical operation on cancer. Among 67 examined, those homozygous alleles revealed a significantly higher incidence...
Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor’s T lymphocytes remains most challenging toxicity allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting overall outcome AML. Here we comprehensively characterized TCR repertoire who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach....
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate better response anti-PD-1 therapies, this association controversial. In study, characterize immune microenvironment tumors, we examined mRNA levels immune-related genes characterized T cell repertoire tumors 13 melanoma...
Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, evaluate immunogenomic dynamics endocrine receptor (ER) positive or triple negative cancer (TNBC). Simon two-stage design indicated at least four from first 18 patients were needed proceed with second stage. T-cell (TCR) sequencing immune-gene...
As the use of next-generation sequencing (NGS) for plasma cell-free DNA (cfDNA) continues to expand in clinical settings, accurate identification circulating tumor mutations is important validate its management cancer patients. Here, we aimed characterize including clonal hematopoiesis (CH)-related cfDNA and tissues using same ultradeep NGS assay evaluate significance CH-related on interpretation liquid biopsy results. Ultradeep targeted Oncomine Pan-Cancer Panel was performed matched...
Abstract Purpose: To achieve eradication of solid tumors, we examined how many neoantigens need to be targeted with T-cell receptors (TCR) by which type T cells. Experimental Design: Unmanipulated, naturally expressed (autochthonous) were adoptively transferred TCR-engineered autologous cells (TCR-therapy). TCR-therapy used CD8+ subsets engineered TCRs isolated from (CD8+TCR-therapy), CD4+ (CD4+TCR-therapy), or combinations both. The tumors established for at least 3 weeks and derived...
Despite long-term clinical experience with docetaxel, unpredictable severe adverse reactions remain an important determinant for limiting the use of drug. To identify a genetic factor(s) determining risk docetaxel-induced leukopenia/neutropenia, we selected subjects who received docetaxel chemotherapy from samples recruited at BioBank Japan, and conducted case-control association study. We genotyped 84 patients, 28 patients grade 3 or 4 56 no toxicity (patients 1 2 were excluded), total 79...
Squamous cell carcinoma of the head and neck (SCCHN) is a relatively common malignancy with suboptimal long-term prognosis, thus new treatment strategies are urgently needed. Over last decade, histone methyltransferases (HMT) have been recognized as promising targets for cancer therapy, but their mechanism action in most solid tumors, including SCCHN, remains to be elucidated. This study investigated role Wolf-Hirschhorn syndrome candidate 1 (WHSC1), an NSD family HMT, SCCHN....
Abstract Purpose: Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination potential genetic drivers offers the possibility improving therapeutic approaches and discovering novel prognostic indicators. Experimental Design: Using pTN staging, we case-matched 81 patients resected ≥pT2 cancers for whom perioperative chemotherapy use disease recurrence status were known. Whole-exome sequencing was conducted 43 cases to identify recurrent...
Abstract Purpose: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded somatic nonsynonymous nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a type of T-cell receptor (TCR) that is specific for AAS. Experimental Design: By exome RNA sequencing an UV-induced tumor, we identified AAS in p68 (mp68), co-activator p53....
The success of cancer immunotherapies has highlighted the potent ability local adaptive immune responses to eradicate cells by targeting neoantigens generated somatic alterations. However, how these factors interact drive natural history muscle-invasive bladder (MIBC) is not well understood.To investigate role regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing tumor-infiltrating T (TILs), silico neoantigen prediction from exome sequences,...
Purpose: Current evolution of cancer immunotherapies, such as immune checkpoint blockade, has implicated neoantigens major targets anticancer cytotoxic T cells. Adoptive T-cell therapy with neoantigen-specific receptor (TCR)-engineered cells would be an attractive therapeutic option for advanced cancers where the host antitumor function is strongly inhibited. We previously developed a rapid and efficient pipeline production TCR-engineered using peripheral blood from HLA-matched healthy...
Abstract Background: Cytochrome P450 2D6 (CYP2D6), one of the most important drug-metabolizing enzymes, has been reported to possess variation in encoding CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6) that affects enzymatic activity. For pharmacogenetic study CYP2D6, accurate measurement dosage functional is essential; however, current genotyping techniques are insufficient because their inability provide exact copy number genes. Methods: We developed 3 quantitative...
To investigate the link between genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations tumor-infiltrating lymphocytes (TILs) malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity TILs (T-cell receptor β (TCRβ) repertoire), expression profiles immune-related genes using specimens three different sites (anterior, posterior, diaphragm) obtained from six MPM patients. Integrated analysis...