東京大学 · 医学
Miki Ando教授の研究室は、がん免疫療法の革新的なアプローチとして、 induced pluripotent stem cell(iPSC)を用いた機能的若返りT細胞の開発を主軸としています。特にEpstein-Barrウイルス関連がんや子宮頸がんに対して、特異的で持続的な抗腫瘍効果を示すrejuvenated T細胞(rejT)の作製とその臨床応用を目指しています。また、腫瘍抗原の逃げを防ぐ二重抗原受容体を搭載したiPSC由来T細胞の開発や、自己免疫拒絶反応を回避するHLA不活性化技術の確立も進んでいます。
Figures are computed from collected data and may differ slightly.
Summary We examined the effectiveness of various anti‐tumour agents to natural killer (NK)‐cell tumour cell lines and samples, which are generally resistant to chemotherapy, using flow cytometric terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labelling (TUNEL) assay. Although NK‐YS and NK‐92 were highly resistant to various anti‐tumour agents, l ‐asparaginase induced apoptosis in these two NK‐cell lines. NK‐cell leukaemia/lymphoma and acute lymphoblastic leukaemia (ALL) samp
We generated dual-antigen receptor (DR) T cells from induced pluripotent stem cells (iPSCs) to mitigate tumor antigen escape. These cells were engineered to express a chimeric antigen receptor (CAR) for the antigen cell surface latent membrane protein 1 (LMP1; LMP1-CAR) and a T cell receptor directed to cell surface latent membrane protein 2 (LMP2), in association with human leucocyte antigen A24, to treat therapy-refractory Epstein-Barr virus-associated lymphomas. We introduced LMP1-CAR into iP
Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited "off-the-shelf" source of therapeutic T cells may be feasible. To generate safer iPSCs, we reprogrammed human papilloma virus type 16 (HPV16) E6-specific CTLs by Sendai virus vector without cotransduction of SV40 large T antigen
The concept of allogeneic cell therapy was first presented over 60 years ago with hematopoietic stem cell transplantation. However, complications such as graft versus host disease (GVHD) and regimen-related toxicities remained as major obstacles. To maximize the effect of graft versus leukemia, while minimizing the effect of GVHD, donor lymphocyte infusion was utilized. This idea, which was used against viral infections, postulated that adoptive transfer of virus-specific cytotoxic T lymphocytes
Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CTL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL <i>in vivo</i> by Epstein-Barr virus-specific iPSC-derived antigen-specif
Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system. To overcome this, we develop HLA-A24&-E dual integrated HPV-rejTs after erasing HLA class
The prognosis of Ewing sarcoma caused by <i>EWS/FLI1</i> fusion is poor, especially after metastasis. Although therapy with CTLs targeted against altered EWS/FLI1 sequences at the gene break/fusion site may be effective, CTLs generated from peripheral blood are often exhausted because of continuous exposure to tumor antigens. We addressed this by generating induced pluripotent stem cell (iPSC)-derived functionally rejuvenated CTLs (rejT) directed against the neoantigen encoded by the <i>EWS/FLI1
Trio-next generation sequencing is useful to identify undiagnosed inherited diseases. We have attended a patient with trigenic <i>ADH5</i>/<i>ALDH2</i>/<i>ADGRV1</i> pathogenic variants, which caused two distinct diseases, myelodysplastic syndrome and Usher syndrome. Whole genome sequencing of peripheral blood from the patient and his parents were applied to identify disease-causing genes. Sanger sequencing was performed to validate the identified <i>ADH5</i>/<i>ALDH2</i>/<i>ADGRV1</i> variants.
Small cell lung cancer (SCLC) is a type of high-grade neuroendocrine carcinoma. It initially responds to chemotherapy but rapidly becomes chemoresistant and it is highly proliferative. The prognosis in SCLC is poor<i>.</i> We have established a novel SCLC cell line, SCLC-J1, from a malignant pleural effusion in a patient with advanced SCLC<i>.</i> SCLC-J1 cells express ganglioside GD2, CD276, and Delta-like protein 3. <i>RB1</i> is lost. These features of the new SCLC cell line may be useful in
ScRNA-seq data reported in this paper is deposited in the Gene Expression Omnibus (GEO) database with accession number GSE272336. Healthy donor CD4+ T-cell dataset was downloaded from the 10x Genomics dataset downloads (https://support.10xgenomics.com/single-cell-gene-expression/datasets/3.0.0/pbmc_10k_protein_v3). Human pancreas dataset (GSE73727) was downloaded from the GEO database.
We describe evolution of persistent immune thrombocytopaenic purpura (ITP) from acute ITP in a young woman with clinically otherwise inapparent severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) infection (COVID-19); her development of ITP was matter for an earlier report.[1] ITP is an acquired disease in which thrombocytopaenia results from autoantibodies against platelet antigens. Approximately 10% of patients with acute ITP develop persistent (lasting 3–12 months) or chronic (>12
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