Neoantigen pulse iPS cell-derived dendritic cell immunotherapy using the own organoids

使用自己的类器官进行新抗原脉冲 iPS 细胞衍生的树突状细胞免疫治疗

• 批准号: 22K16498
• 负责人: 北谷 純也
• 金额: $ 3万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K16498/
• 关键词: オルガノイド; iPS細胞; 樹状細胞; ネオアンチゲン; 癌免疫療法

担癌患者においては、免疫の司令塔である樹状細胞の成熟能や抗原提示能の低下を呈することが知られている。これらの樹状細胞療法の弱点を克服するために、iPS細胞に着目し、iPS細胞由来樹状細胞 (iPSDCs) を用いた癌ワクチン療法の基礎研究を行ってきた。本研究の目的は、正常細胞には発現せず、腫瘍における遺伝子変異によってのみ発現するネオアンチゲンを標的としたiPSDCsの作成を行い、消化器固形癌に対する根治を目指した個別化癌ワクチン療法の開発を目的としている。まずは、この治療モデルの確立と治療効果の比較を行う細胞傷害活性のコントロールの設定のため、健常人での共通抗原を用いた研究を実施した。研究への参加の同意が得られた3名の健常人ドナーの末梢血単核球から山中4因子を導入することでiPS細胞を樹立し、分化誘導したiPSDCsに胃癌、大腸癌で発現率が高いMesothelin遺伝子をアデノウイルスベクターを用い遺伝子導入した。遺伝子の導入効率は約40％であった。Mesothelin遺伝子導入iPSDCsの成熟能に関しては、MoDCsのそれと類似するものであった。このMesothelin遺伝子導入iPSDCsにより刺激して得られたCTLsは、自己仮想targetであるMesothelin遺伝子導入LCL(lymphoblastoid cells)に対し、抗原特異的な細胞傷害活性をいずれのドナーでも示すことを証明した。その後、担癌患者のiPS樹立およびオルガノイド作成に関しては、本学の倫理委員会の承認を受け作成に取りかかっている。

In patients with burden cancer, the antigen of the mature cells in the command tower of immunity and the command tower of immunity suggests that they can be "low". The weakness of the cell method is to overcome the weakness of the cell method, to overcome the weakness of the cell method. In this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the objectives of this study are as follows: in this study, the purpose of this study is to develop a method for the treatment of solid cancer of the digestive apparatus. The results of diagnosis and treatment were compared with those of normal people, and the common antigens of normal people were used in the study of common antigen. The participants in the study agreed that there were 3 normal people, peripheral blood nuclear globules, 4 factors in the mountain, iPS cells, differentiation factors, iPSDCs gastric cancer, large cancer, high risk of Mesothelin cancer, large cancer, high risk of gastric cancer and cancer. The admission rate is about 40%. When Mesothelin is imported into iPSDCs, it is possible to detect errors, and the type of MoDCs diagnosis is similar to that of normal users. The Mesothelin was inserted into the iPSDCs and the stimulation was obtained. I wanted to target the Mesothelin into the LCL (lymphoblastoid cells) virus, and the antigen specific cell damage activity was detected by the antigen. After the treatment, the patients with cancer will be treated with iPS, and the committee will confirm that the patients will receive the cancer and get it.

项目成果

Induced pluripotent stem cell-derived dendritic cell vaccine therapy genetically modified on the ubiquitin-proteasome system

• DOI: 10.1038/s41434-023-00388-z
• 发表时间: 2023-03-23
• 期刊: GENE THERAPY
• 影响因子: 5.1
• 作者: Tominaga，Shinta;Ojima，Toshiyasu;Yamaue，Hiroki
• 通讯作者: Yamaue，Hiroki