Immunotherapy for Chronic Lymphocytic Leukemia

慢性淋巴细胞白血病的免疫治疗

• 批准号: 6761375
• 负责人: JANUARIO E CASTRO
• 金额: $ 13.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6761375
• 关键词: 2' 3' dideoxynucleoside; Adenoviridae; B lymphocyte; CD1 molecule; antigen presentation; chronic lymphocytic leukemia; clinical research; clone cells; combination cancer therapy; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; flow cytometry; histocompatibility antigens; human tissue; immunomodulators; interferon gamma; leukocyte activation /transformation; leukocyte count; neoplasm /cancer immunotherapy; oligonucleotides; peptide library; therapy design /development; western blottings

DESCRIPTION (provided by applicant): Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults and is characterized in many cases by a progressive clinical course in which conventional treatments, such as chemotherapy, may palliate symptoms but unfortunately do not provide an established cure. Therefore, there is an urgent need for new and more effective therapeutic strategies that involve different mechanisms of action. Several features of this disease suggest that immune-based strategies may have therapeutic potential. Therefore, our group has developed strategies that enhance the ability of CLL cells to interact with T cells and promote effective anti-leukemia responses through a mechanism of Enhanced Antigen Presentation. One is the use of in vitro transduction of CLL cells using adenovirus encoding CD154 (Ad-CD154). This approach has proven to be effective in a recently completed clinical trial in which patients treated with this modality had increased T cell counts, decreased lymph node size and fewer circulating leukemia cells. A second immune-based strategy in CLL is the use of DNA oligodeoxynucleotides (ODN), which activates CLL cells, enhances their function as antigen presenting cells and most importantly improves infectibility and transgene expression of Ad-CD 154. The proposal presented here will investigate the mechanism of ODN mediated activation in CLL cells and the potential synergistic effect in combination with Ad-CD154. Also, we will use this model of Enhanced Antigen Presentation to expand and clone reactive/cytolytic anti-leukemia T cells from CLL patients. Using Positional Scanning Synthetic Combinatorial Peptide Libraries, we propose to characterize specific peptide ligands to those reactive/cytolytic T cells.

描述（由申请人提供）：慢性淋巴细胞白血病（CLL）是成人中最常见的白血病，在许多病例中，其特点是一个渐进的临床过程，其中常规治疗，如化疗，可能缓解症状，但不幸的是，不能提供一个确定的治愈方法。因此，迫切需要新的和更有效的治疗策略，涉及不同的作用机制。