- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Glaucoma and retinal disorders
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Renal and related cancers
- Chronic Lymphocytic Leukemia Research
- vaccines and immunoinformatics approaches
- Pharmacy and Medical Practices
- Head and Neck Cancer Studies
- Acute Lymphoblastic Leukemia research
- Head and Neck Surgical Oncology
- Microbial Natural Products and Biosynthesis
- Retinal Diseases and Treatments
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Biomedical and Engineering Education
- Animal Disease Management and Epidemiology
Nagasaki University
2016-2025
Kyoto University
2020-2025
Yokohama City University Hospital
2025
Yokohama City University
2025
Mie University
2011-2024
Yamaguchi University
2024
Kyoto Pharmaceutical University
2020-2021
Hiroshima University
1982-2020
Keio University
2016-2020
Sapporo City General Hospital
2018
Fibroblastic tumour stroma comprising mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) promotes the invasive metastatic properties of cells. Here we show that activated CD8+ T cell-derived extracellular vesicles (EVs) interrupt fibroblastic stroma-mediated progression. Activated from healthy mice transiently release cytotoxic EVs causing marked attenuation invasion metastasis by apoptotic depletion stromal Infiltration EV-producing is observed in neovascular areas with...
Adoptive T-cell therapy using lymphocytes genetically engineered to express tumor antigen-specific TCRs is an attractive strategy for treating patients with malignancies. However, there are potential drawbacks this strategy: mispairing of the introduced TCR alpha/beta chains endogenous subunits and competition CD3 molecules between can impair cell surface expression transduced TCR, resulting in insufficient function generation autoreactive T cells. In addition, risk development following...
Abstract Purpose: Preparative lymphodepletion, the temporal ablation of immune system, has been reported to promote persistence transferred cells along with increased rates tumor regression in patients treated adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy receptor (TCR) gene–engineered T cells. Experimental Design: We conducted a first-in-man clinical trial TCR gene-transduced transfer recurrent MAGE-A4–expressing esophageal...
Abstract Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating immunoediting process. We observe that, several mouse models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma CMS5 MCA-induced fibrosarcoma naturally...
Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, the mechanisms underlying tumor immune resistance not been fully elucidated. By comparing microenvironment inhibition–sensitive –resistant murine tumors, we observed that resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+...
Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001. Patients with advanced/metastatic esophageal were enrolled subcutaneously vaccinated either 100 μg or 200 NY-ESO-1 protein complexed CHP. The primary endpoints safety humoral responses, secondary endpoint was efficacy. A total 25 enrolled. Thirteen twelve repeatedly...
Because of the shortage ideal cell surface antigens, development T-cell receptor (TCR)-engineered T cells (TCR-T) that target intracellular antigens such as NY-ESO-1 is a promising approach for treating patients with solid tumors. However, endogenous TCRs in vector-transduced have been suggested to impair cell-surface expression transduced TCR while generating mispaired can become self-reactive.
Abstract Since the first approval of an immune-checkpoint inhibitor, we have witnessed clinical success cancer immunotherapy. Adoptive T-cell therapy with chimeric antigen-receptor T (CAR-T) cells has shown remarkable efficacy in hematological malignancies. Concurrently these successes, immunoediting concept that refined immunosurveillance underpinned scientific mechanism and reason for past failures, as well recent breakthroughs Now, face next step issues to be solved this field, such tumor...
A variety of tumor-derived antigens have been defined by IgG antibodies in tumor bearers' sera with serological identification recombinant expression cloning (SEREX), a method. The majority these show no structural abnormality and seem to be wild-type autoantigens. Coimmunization DNA encoding autoantigens tumor-specific cytotoxic T lymphocytes epitopes heightened CD8+ cell responses increased resistance challenge CD4+ cell-dependent manner. In contrast, immunization SEREX-defined alone leads...
Abstract In this analysis, we examined whether peptides derived from a wild-type murine proto-oncogene, c-erbB-2, function as tumor rejection Ags. Expression of c-erbB-2 by means reverse transcription-PCR was observed in several normal adult tissues, such intestine, kidney, and testis. We then transduced human cDNA into two mutually noncross-reactive fibrosarcoma lines BALB/c origin, CMS7 CMS17. mice immunized with CMS17HE (CMS17 cDNA), the growth subsequently challenged CMS7HE (CMS7 cDNA)...
The antigenic targets recognized by naturally occurring CD4+ CD25+ regulatory T cells (T reg cells) have been elusive. We serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas serological identification antigens recombinant expression cloning (SEREX). mice immunized with SEREX-defined had strong suppressive activity on peptide-specific proliferation CD25− and CD8+ cells. effect was observed without in vitro cell stimulation. Foxp3...
Abstract Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) exhibit potent immunostimulating activity by binding with Toll-like receptor 9 (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation into CD11c+ dendritic cells (DCs) and induces enhanced serum interleukin (IL)-12 levels compared unmodified CpG-ODN. CpG-liposome potently activated natural killer (NK) (84.3%)...
The process of cancer immunoediting generates a repertoire cells that can persist in immune-competent hosts. In its most complex form, this begins with the elimination highly immunogenic unedited tumor followed by escape less edited cells. Although tumors release immunosuppressive factors, it is unknown whether produce cytokines enhance antitumor function. Utilizing gene microarray analysis, we found cytokine interleukin 17D (IL-17D) was expressed certain but not mouse cell lines. Moreover,...
We show that it is feasible to monitor the synchronized population spikes of thalamocortical axonal terminals and cortical neurons outside brain using high-resolution magnetoencephalography (MEG). Electrical stimulation snout elicited somatic-evoked magnetic fields (SEFs) above primary somatosensory cortex (SI) piglet. The SEFs contained high-frequency oscillations (HFOs) around 600 Hz similar in many respects noninvasively measured HFOs from humans with MEG electroencephalography (EEG)....
Abstract Immunization with serological identification of Ags by recombinant expression cloning (SEREX)-defined self-Ags leads to generation/activation CD4+CD25+ regulatory T cells suppressive activities and enhanced Foxp3. This is associated increased susceptibility pulmonary metastasis following challenge syngeneic tumor development 3-methylcholanthrene-induced primary tumors. In contrast, coimmunization the same SEREX-defined mixed a CTL epitope results in augmented activity heightened...