Phase I, Open-Label Dose-Escalation

第一阶段，开放标签剂量递增

• 批准号: 7667512
• 负责人: JANUARIO E CASTRO
• 金额: $ 20万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7667512
• 关键词: Phase; Open; Label; Dose; Escalation

DESCRIPTION (provided by applicant): Chronic lymphocytic leukemia is the most common adult leukemia in Western societies with 10,000 cases diagnosed in the United States every year and a prevalence of approximately 80,000 cases (US Estimated 28-Year Limited-Duration Prevalence on 1/1/2003) (http://seer.cancer.gov/). Although much has been learned about the genetics, biochemistry and immunology of this disease, CLL still is considered incurable, mandating development of improved treatment strategies. Like other cancers, CLL cells harbor genetic changes that apparently play a role in the pathogenesis or progression of this disease. Such alterations, along with the clonal expression of somatically generated immunoglobulin genes, may direct expression of "altered-self" proteins that could be targeted by the patient's immune system. Strategies that can induce such immune responses against autologous leukemia cells may be effective in the treatment of this disease. The investigators propose to evaluate the pre-clinical and clinical activity of a new modality of immuno-gene therapy mediated by transduction of leukemia cells with CD154 (CD40 Ligand) using direct intra-lymph node (intranodal) injection of a replication-defective adenovirus vector that encodes a chimeric (human-mouse) CD154 molecule (Ad-ISF35). Direct intranodal injection of Ad-ISF35 may prove to be an effective and less expensive strategy to transduce cancer cells and induce anti-tumor responses compared with the current protocols that we are using in which ex-vivo manipulation of the leukemia/ lymphoma cells is required. The support obtained from this grant will facilitate Phase 1 clinical data that is essential for the development of this therapeutic strategy in CLL and its potential applications to other types of cancer.

描述（由申请人提供）： 慢性淋巴细胞性白血病是西方社会中最常见的成年白血病，每年在美国诊断出10,000例病例，大约80,000例病例（美国估计在2003年1月1日为28年有限寿命患病率（http://seer.cancer.gov/）。 尽管已经了解了这种疾病的遗传学，生物化学和免疫学，但CLL仍然被认为是无法治愈的，这是强制性发展的治疗策略。 像其他癌症一样，CLL细胞具有遗传变化，显然在该疾病的发病机理或进展中起作用。 这种改变，以及体外产生的免疫球蛋白基因的克隆表达，可以指导患者的免疫系统可以靶向的“改变自身”蛋白。 可以诱导这种免疫反应对自体白血病细胞的策略可能有效治疗该疾病。 研究人员建议使用直接使用Replication-lymph node（Intanodal）注入复制抑制的adenevector（AD-1）CD154（cD154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154）（cd154），提议通过CD154（CD40配体）转导白血病细胞（CD40配体）介导的新型免疫 - 基因治疗方法的临床前和临床活性。 与我们使用的当前使用的方案相比，直接的AD-FISF35的直接注射AD-ISF35可能是转导癌细胞并诱导抗肿瘤反应的有效且较便宜的策略。 从该赠款获得的支持将促进1阶段临床数据，这对于在CLL中开发这种治疗策略及其在其他类型的癌症中的潜在应用至关重要。