PHASE I/II STUDY OF ANTI-CTLA-4 MONOCLONAL ANTIBODY (MDX-010) IN FOLLICULAR N

滤泡中抗 CTLA-4 单克隆抗体 (MDX-010) 的 I/II 期研究

• 批准号: 7606794
• 负责人: John M Timmerman
• 金额: $ 0.48万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-21 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606794
• 关键词: Antibodies; Antigens; Autologous Tumor Cell; B-Cell NonHodgkins Lymphoma; Biopsy; CD8B1 gene; Clinic; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Follicular Lymphoma; Funding; Grant; Immune; In Vitro; Institution; Lymphocyte Subset; Measurable; Measurement; Monoclonal Antibodies; Numbers; Patients; Phase; Population; Relapse; Research; Research Personnel; Resistance; Resources; Safety; Sampling; Source; T memory cell; T-Lymphocyte; United States National Institutes of Health; Vaccinated; Vaccine Therapy; clinical efficacy; cytokine; cytotoxicity; killings; peripheral blood; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aim 1. Perform a phase I/II clinical trial to characterize the safety and clinical efficacy of anti-CTLA-4 monoclonal antibody in patients with follicular B cell non-Hodgkin's lymphoma. This multi-center study (UCLA and Mayo Clinic) will include 36 patients with measurable follicular lymphoma relapsing after or resistant to conventional therapies. We theorize that CTLA-4 blockade will have clinical anti-tumor effects in this disease setting, particularly in patients who have received prior tumor-specific vaccine therapy. Previously vaccinated patients will represent one-half of subjects. Specific Aim 2. Determine whether anti-CTLA-4 treatment results in systemic recruitment of anti-tumor immune effector mechanisms in patients with follicular lymphoma. Before and after therapy, peripheral blood will be sampled for measurement of: 1) Tumor-specific cytokine release and cytotoxicity, 2) Responsiveness of memory T cells to stimulation with recall antigens, 3) The numbers and activation state of circulating T cells, including the CD4+CD25+ regulatory T cell population which constitutively expresses CTLA-4, and 4) Tumor-specific antibodies. Specific Aim 3. Investigate whether anti-CTLA-4 therapy can boost the number and function of T cell effectors in the tumor microenvironment. Tumors will be biopsied pre- and post-treatment to characterize the number and activation state of tumor-infiltrating lymphocyte subpopulations (including CD4+, CD8+, and CD4+CD25+ regulatory T cells), and to evaluate the ability of in vitro-expanded tumor-infiltrating T cells to recognize and kill autologous tumor cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 具体目标 1. 进行 I/II 期临床试验，以表征抗 CTLA-4 单克隆抗体在滤泡 B 细胞非霍奇金淋巴瘤患者中的安全性和临床疗效。 这项多中心研究（加州大学洛杉矶分校和梅奥诊所）将纳入 36 名患有可测量的滤泡性淋巴瘤的患者，这些患者在传统疗法后复发或对传统疗法产生耐药性。 我们推测 CTLA-4 阻断在这种疾病中将具有临床抗肿瘤作用，特别是对于先前接受过肿瘤特异性疫苗治疗的患者。 先前接种过疫苗的患者将占受试者的一半。 具体目标 2. 确定抗 CTLA-4 治疗是否会导致滤泡性淋巴瘤患者抗肿瘤免疫效应机制的系统性募集。 治疗前后，将采集外周血样本以测量：1）肿瘤特异性细胞因子释放和细胞毒性，2）记忆T细胞对记忆抗原刺激的反应性，3）循环T细胞的数量和激活状态，包括组成型表达CTLA-4的CD4 + CD25 +调节性T细胞群，以及4）肿瘤特异性抗体。 具体目标 3. 研究抗 CTLA-4 治疗是否可以增强肿瘤微环境中 T 细胞效应细胞的数量和功能。 在治疗前和治疗后对肿瘤进行活检，以表征肿瘤浸润淋巴细胞亚群（包括CD4+、CD8+和CD4+CD25+调节性T细胞）的数量和激活状态，并评估体外扩增的肿瘤浸润T细胞识别和杀伤自体肿瘤细胞的能力。