AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR LYMPHOMA--IMMUNOTHERAPY

自体骨髓移植治疗淋巴瘤--免疫治疗

• 批准号: 6236432
• 负责人: DANIEL J WEISDORF
• 金额: $ 2.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-01-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236432
• 关键词: Hodgkin's disease; autologous transplantation; bone marrow transplantation; cell mediated lymphocytolysis test; clinical trials; disease /disorder model; extracellular matrix; hematopoietic stem cells; human subject; immunochemistry; immunofluorescence technique; laboratory mouse; neoplasm /cancer immunotherapy; neoplasm /cancer relapse /recurrence; nonHodgkin's lymphoma; tissue /cell culture

Autologous marrow transplantation for non-Hodgkin's lymphoma and Hodgkin's disease has produced extended disease-free survival for some patients but malignant relapse remains the most frequently reported cause of post-transplant treatment failure. In this proposal we will investigate clinical and laboratory initiatives designed to reduce the incidence of malignant relapse after transplantation by the application of immunotherapy. The clinical studies proposed include the continuation of an ongoing randomized trial comparing bone marrow stem cells versus peripheral blood stem cells for hematologic and immunologic reconstitution following transplantation. Because there may be differential contamination of blood versus marrow with clonogenic tumor cells, we will also assess this controlled trial for differences in disease-free survival. We will also conduct a Phase I and follow-up Phase II trial of infusional recombinant human interleukin-1 alpha given during the first 14 days following BMT to promote hematologic and immunologic recovery and provide immunologically based anti-tumor responses. In addition, we propose to conduct a Phase II trial seeking efficacy for recombinant human IL-2 given by continuous infusion during the first three weeks following autologous transplantation, in promoting immunologic activation and antineoplastic activity. In related, developmental laboratory studies we propose to explore: the use of the cytokines IL-1 alpha and IL-2 to define their antineoplastic effectiveness against human and murine lymphoma cell lines; to explore their utility in generating effector cells capable of killing these lymphoma targets in vitro; to generate effectors capable of adhering to extracellular matrix proteins and homing towards tumor sites in vivo; and finally, to explore the use of these cytokines' and cytotoxic effector cells' ability to improve survival in vivo in severe combined immunodeficiency (SCID) mice with human lymphomas and normal mice with lymphoma undergoing syngeneic BMT. These laboratory studies are designed to allow us to develop new clinical strategies for more effective immunotherapy accompanying autologous marrow transplantation in order to prevent malignant relapse and improve overall patient survival.

非霍奇金淋巴瘤和霍奇金的自体骨髓移植 疾病已经为某些患者产生了延长的无病生存期，但是 恶性复发仍然是最常报道的原因 移植后治疗失败。 在此提案中，我们将调查 旨在减少发生率的临床和实验室计划 通过应用移植后恶性复发 免疫疗法。 提出的临床研究包括继续 正在进行的随机试验比较骨髓干细胞与 血液学和免疫学重建的外周血干细胞 移植后。 因为可能存在差异污染 血液与克隆性肿瘤细胞的骨髓，我们还将评估 这项对无疾病生存差异的对照试验。 我们将 还进行了I期和输注的随访II期试验 重组人白介素-1α在最初的14天内给出 遵循BMT促进血液学和免疫恢复并提供 基于免疫学的抗肿瘤反应。 此外，我们建议 进行II期试验，以寻求重组人IL-2有效性 自体后的前三周连续输注 移植，促进免疫学激活和抗肿瘤 活动。 在相关的发展实验室研究中，我们建议 探索：使用细胞因子IL-1 alpha和IL-2定义它们的使用 针对人和鼠淋巴瘤细胞系的抗肿瘤有效性； 探索他们在产生能够杀死的效应细胞的效用 这些淋巴瘤在体外靶向；产生能够粘附的效应器 在体内向细胞外基质蛋白和朝向肿瘤部位的归巢； 最后，探索这些细胞因子和细胞毒性效应器的使用 细胞在严重的合并中改善体内生存的能力 具有人淋巴瘤和正常小鼠的免疫缺陷（SCID）小鼠 淋巴瘤正在接受合成性BMT。 这些实验室研究是设计的 使我们能够制定新的临床策略以提高有效性 伴随自体骨髓移植的免疫疗法 防止恶性复发并改善总体患者生存。