VACCINE FOR PATIENTS WITH NON HODGKINS LYMPHOMA

非霍奇金淋巴瘤患者的疫苗

• 批准号: 6166390
• 负责人: STEVEN H BERNSTEIN
• 金额: $ 15.82万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-18 至 2002-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6166390
• 关键词: clinical research; cytotoxic T lymphocyte; delayed hypersensitivity; dendritic cells; enzyme linked immunosorbent assay; human subject; human therapy evaluation; interferon gamma; lymphocyte; monocyte; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; nonHodgkin's lymphoma; tumor antigens; vaccine development

These investigators propose to clone and sequence the VH regions from lymphoma-associated immunoglobulin from fresh lymph node tissue from patients with recurrent lymphoma. They will chose a peptide sequence of 25-mer from the VH region based on its inclusion of 9 mers having optimal MHC peptide binding capacity using a bio-informatics approach based on predictions using binding motifs established for specific HLA-1 alleles expressed by the patient. The peptide will be synthesized and used to "pulse" dendritic cells enriched from the peripheral blood generated in vivo by treatment with FLT-3 ligand. They anticipate that the multiple antigen presenting cell populations within the DC peripheral blood will process and present a wide spectrum of antigens in the context of MHC class I leading to a broad CD8 + T cell response generated against tumor-associated immunoglobulin, and therefore, the tumor. They anticipate evaluating five patients per year for two years. They will determine the safety and feasibility of the in vivo generation of DC from peripheral blood in this patient population, they will determine the safety and feasibility of vaccination with tumor VH peptide pulsed DC, and determine the clinical and immunologic response of vaccination with the tumor VH peptide pulsed DC from peripheral blood from patients with lymphoma.

这些研究人员建议克隆和测序VH区， 来自淋巴瘤相关免疫球蛋白，来自 复发性淋巴瘤患者。他们将选择一个25聚体的肽序列 基于其包含具有最佳MHC肽的9聚体， 结合能力使用生物信息学方法，基于使用 为患者表达的特异性HLA-1等位基因建立的结合基序。 该肽将被合成并用于“脉冲”富集的树突细胞。 来自通过用FLT-3配体处理在体内产生的外周血。 他们预计，体内的多种抗原呈递细胞群 DC外周血将处理并呈递广谱抗原， MHC I类的背景导致产生广泛的CD 8 + T细胞应答， 对抗肿瘤相关免疫球蛋白，从而对抗肿瘤他们 预计每年评估五名患者，持续两年。他们将决定 从外周血中体内产生DC的安全性和可行性 在这一患者人群中，他们将确定安全性， 用肿瘤VH肽脉冲的DC进行疫苗接种的可行性，并确定 用肿瘤VH肽接种的临床和免疫应答 来自淋巴瘤患者外周血的脉冲DC。