Adoptive T Cell Therapy Following Lymphodepletion

淋巴细胞清除后的过继 T 细胞治疗

基本信息

批准号：
6765955
负责人：
Cassian Yee
金额：
$ 33.14万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6765955
关键词：
autologous transplantation cell proliferation cellular immunity clinical research clinical trial phase I cytotoxic T lymphocyte dendritic cells enzyme linked immunosorbent assay fludarabine human subject human therapy evaluation immunotherapy immunotoxicity interleukin 2 leukocyte depletion therapy melanoma passive immunization patient oriented research

项目摘要

DESCRIPTION (provided by applicant): The identification of potential tumor rejection antigens recognized by autologous T cells has spawned numerous clinical trials that target melanoma cells expressing these antigens. Adoptive T cell therapy, involving the isolation and ex vivo expansion of antigen-specific T cell clones for infusion provides for rigorous control over the magnitude, specificity and phenotype of the intended immune response so that the requirements for successful tumor eradication can be clearly defined. Preliminary results using this approach for the treatment of patients with metastatic melanoma in a Phase I clinical trial have demonstrated that adoptive T cell therapy using antigen-specific CD8+ CTL clones, persist in vivo, traffic to tumor sites and can mount a specific immune response with favorable clinical outcomes. Obstacles to more effective therapy were found to be a limited duration of in vivo persistence that was only partially extended with low-dose IL-2. Due to the counter-regulatory effects and cumulative toxicities of IL-2 with prolonged administration, an alternative strategy would be highly desirable. Based on the observation that CD8+ T cells undergo homeostatic proliferation and expansion in a lymphodepleted host, we propose to evaluate in a Phase I clinical trial, the safety, duration of in vivo persistence and anti-tumor effect of adoptively transferred CD8+ antigen-specific CTL clones following fludarabine-mediated lymphodepletion in patients with metastatic melanoma.

描述（由申请人提供）：自体T细胞识别的潜在肿瘤排斥抗原的鉴定已经产生了许多靶向表达这些抗原的黑色素瘤细胞的临床试验。通过抗原特异性T细胞克隆的隔离和离体扩展进行输注的养殖T细胞疗法，可以严格控制预期免疫反应的大小，特异性和表型，从而可以清楚地定义成功消除肿瘤的要求。在I期临床试验中，使用这种方法治疗转移性黑色素瘤患者的初步结果表明，使用抗原特异性CD8+ CTL克隆的产物T细胞疗法，持续体内，肿瘤部位的流量，可以安装特定的免疫反应并具有良好的临床临床效果。发现更有效的治疗的障碍是体内持久性的持续时间有限，仅在低剂量IL-2上部分扩展。由于IL-2随着延长的给药的反调节作用和累积毒性，因此非常需要另一种策略。 Based on the observation that CD8+ T cells undergo homeostatic proliferation and expansion in a lymphodepleted host, we propose to evaluate in a Phase I clinical trial, the safety, duration of in vivo persistence and anti-tumor effect of adoptively transferred CD8+ antigen-specific CTL clones following fludarabine-mediated lymphodepletion in patients with metastatic melanoma.