Functional analysis of cancer-specific human T cells in NOG mice : Cell interaction of CD4, CD8 cells

NOG 小鼠中癌症特异性人类 T 细胞的功能分析：CD4、CD8 细胞的细胞相互作用

• 批准号: 22890084
• 负责人: WANG Linan
• 金额: $ 1.96万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22890084/
• 关键词: MAGE-A4; NOG mouse; CEA; T-body; TCR; scFv

Adoptive cell therapy(ACT) for cancer, in which T cells are collected from patient's peripheral blood, modified by the transduction of tumor-antigen specific T cell receptor(TCR) and re-administered to the same patient, is increasingly the subject of clinical trials. In this study, we aimed to establish a mouse model to analyze "in vivo" functions of the transferred T cells by utilizing immunocompromised(NOG) mice. We observed the regression of transplanted human esophageal tumor(HLA-A2402+, MAGE-A4+) growth only when T cells modified to express TCR, recognizing MAGE-A4(p143-151) peptide in the context of HLA-A2402, were co-administered. This model will provide us more detailed information about mechanism of efficacies of transferred T cells.

用于癌症的免疫细胞疗法（ACT）越来越成为临床试验的主题，其中T细胞从患者的外周血收集，通过肿瘤抗原特异性T细胞受体（TCR）的转导进行修饰，并重新施用给同一患者。在本研究中，我们的目的是建立一个小鼠模型来分析“体内”功能的转移T细胞通过利用免疫功能低下（NOG）小鼠。我们观察到移植的人食管肿瘤（HLA-A2402+，MAGE-A4+）生长的消退仅当共施用经修饰以表达TCR（在HLA-A2402的背景下识别MAGE-A4（p143-151）肽）的T细胞时。这一模型将为我们提供关于转移T细胞的功效机制的更详细的信息。

项目成果

T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice

• DOI: 10.1111/j.1349-7006.2011.02111.x
• 发表时间: 2012-01-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Shirakura, Yoshitaka;Mizuno, Yukari;Shiku, Hiroshi
• 通讯作者: Shiku, Hiroshi

Intracellular Tumor-Associated Antigens Represent Effective Targets for Passive Immunotherapy

• DOI: 10.1158/0008-5472.can-11-3072
• 发表时间: 2012-04-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Noguchi, Takuro;Kato, Takuma;Nishikawa, Hiroyoshi
• 通讯作者: Nishikawa, Hiroyoshi