Allo Stem Cell Transplant as Immunotherapy for Melanoma

同种异体干细胞移植作为黑色素瘤的免疫疗法

• 批准号: 6522680
• 负责人: JOHN A THOMPSON
• 金额: $ 31.14万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-20 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522680
• 关键词: histocompatibility antigens; homologous transplantation; human subject; human therapy evaluation; melanoma; metastasis; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; patient oriented research; stem cell transplantation; tumor antigens

DESCRIPTION (Provided by applicant): Current treatments for metastatic melanoma are unsatisfactory, as very few patients achieve durable complete remissions. This project explores a novel concept for delivering immunotherapy, via nonmyeloablative allogeneic stem cell transplantation (Allo SCT). We hypothesize that the establishment of donor hematopoietic chimerism will induce a graft-versus-tumor (GVT) effect. A growing list of antigens have been identified on melanoma cells, which may elicit Class I or Class II T cell responses. The mechanism of GVT effect after Allo SCT is under intense scrutiny, and may involve T cell reactivity to minor histocompatibility antigens, as well as to tumor specific antigens. The Specific Aims of this proposal are: 1. Complete the first stage of a Phase II trial (FHCRC protocol 1462) of Allo SCT in patients with metastatic melanoma, to determine the clinical efficacy (as assessed by the objective response rate and survival) and toxicity (including graft-versus-host disease). Up to 15 patients with metastatic melanoma, who have achieved partial remission, minor remission, or stable disease after initial systemic therapy, will be treated. Eligible patients will receive low-dose total body irradiation (200cGy), and fludarabine, followed by infusion of peripheral blood stem cells from a HLA matched sibling donor, with post-transplant cyclosporine and mycophenylate mofetil. Subsequently, selected patients will receive donor lymphocytes to augment the GVT effect. 2. Evaluate immune responses, in patients undergoing Allo SCT, to known melanoma antigens, novel tumor-specific antigens, tissue-specific antigens, and minor histocompatibility antigens. The CD4+ and CD8+ T cell responses to defined peptides will be assessed by tetramer analysis, cytolytic effector function, and proliferative reactivity. Evaluation of the potential response, safety of Allo SCT, and elucidation of these T-cell responses will facilitate the development of future studies to manipulate GVT effect in patients with metastatic melanoma.

描述（由申请人提供）：当前的转移性黑色素瘤治疗方法不令人满意，因为很少有患者可以完成持久的完全缓解。 该项目通过 非元素同种异体干细胞移植（Allo SCT）。我们 假设建立供体造血嵌合体将诱发 移植物肿瘤（GVT）效应。越来越多的抗原清单 在黑色素瘤细胞上鉴定，可能会引起I类或II类T细胞 回答。 Allo SCT之后的GVT效应机制非常强烈 审查，可能涉及T细胞对较小组织相容性的反应性 抗原以及特异性抗原。这个特定的目的 提案是： 1。完成Allo的II期试验（FHCRC协议1462）的第一阶段 转移性黑色素瘤患者的SCT，以确定临床功效 （根据客观响应率和生存率评估）和毒性 （包括移植物与宿主病）。最多15例转移性患者 黑色素瘤，已经达到了部分缓解，轻微缓解或稳定 初始全身治疗后的疾病将接受治疗。合格的患者会 接受低剂量的全身照射（200cgy）和Fludarabine，其次是 从HLA匹配的兄弟姐妹供体中输注外周血干细胞， 移植后环孢霉素和霉酚酸莫菲蒂。随后选择 患者将接受供体淋巴细胞以增加GVT效应。 2。在接受Allo SCT的患者中评估免疫反应 黑色素瘤抗原，新型肿瘤特异性抗原，组织特异性抗原和 较小的组织相容性抗原。 CD4+和CD8+ T细胞对 定义的肽将通过四聚体分析，细胞溶解效应子进行评估 功能和增殖反应性。 评估潜在响应，Allo SCT的安全性和阐明 这些T细胞的反应将促进未来研究的发展 转移性黑色素瘤患者的操纵GVT效应。