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: 7717985
• 负责人: John M Timmerman
• 金额: $ 0.11万
• 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: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717985
• 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 具体目标1。执行I/II期临床试验，以表征抗CTLA-4单克隆抗体对卵泡B细胞非霍奇金淋巴瘤患者的安全性和临床功效。 这项多中心研究（UCLA和Mayo诊所）将包括36例可测量的卵泡淋巴瘤在后复发或抗性常规疗法的患者。 我们认为CTLA-4封锁将在这种疾病中具有临床抗肿瘤作用，尤其是在接受过肿瘤特异性疫苗疗法的患者中。 以前接种疫苗的患者将代表一半受试者。 具体目标2。确定抗CTLA-4治疗是否导致卵泡淋巴瘤患者的抗肿瘤免疫效应机制的全身募集。 治疗前后，将对外周血进行测量：1）肿瘤特异性细胞因子释放和细胞毒性，2）记忆T细胞对用回忆抗原刺激的反应性，3）3）循环T细胞的数量和激活状态，包括CD4+ CD25+ CD25+ CD25+ CD25+ CD25+调节性T细胞群，这些cd25+ cd25+ CD25+ cdib sprificience contecibific thumeratific thumer contecific thumor contec tula tum c.tla-4 and 4）和4）和4）。 具体目的3。研究抗CTLA-4治疗是否可以增加肿瘤微环境中T细胞效应子的数量和功能。 肿瘤将进行活检前和治疗后，以表征肿瘤浸润的淋巴细胞亚群的数量和激活状态（包括CD4+，CD8+和CD4+CD4+CD25+调节性T细胞），并评估体内膨胀的肿瘤摄入肿瘤细胞的能力，以识别自身抑制自身的肿瘤细胞。