THERAPEUTIC DNA VACCINES TO TREAT B CELL LYMPHOMA

治疗 B 细胞淋巴瘤的治疗性 DNA 疫苗

• 批准号: 6325672
• 负责人: PETER M. HOBART
• 金额: $ 28.15万
• 依托单位: VICAL, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325672
• 关键词: B cell lymphoma; Macaca mulatta; antiidiotype antibody; colony stimulating factor; hybrid antibody; laboratory mouse; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; plasmids; technology /technique development; transfection /expression vector; vaccine development; vector vaccine

We propose a series of experiments which evaluate methods to increase potency of a plasmid DNA tumor vaccine being developed for the treatment of low grade non-follicular lymphoma. Based on the results of pre-clinical tumor challenge studies in a mouse lymphoma model system and a Phase I/II clinical trial in B-cell lymphoma patients, we have demonstrated that a novel bicistronic plasmid DNA vector, designed to elicit an anti-idiotype immune response when injected into muscle tissue, can protect animals from idiotype tumor cell challenge and can generate immunogenicity in humans. More recent pre-clinical studies indicate that co-injection of a second DNA plasmid, expressing the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increases immunogenicity and long-term protection in animals relative to the idiotype expression plasmid alone. The series of pre-clinical experiments presented here are designed to further increase the potency of this multivalant plasmid vaccine in mice and, in turn, rhesus monkeys. We anticipate that these experiments will lead to a more potent tumor vaccine which will be tested in B-cell lymphoma patients in a second clinical trial. We also anticipate that success of this therapeutic vaccine will lead to the use of DNA vaccines to treat a wide range of human cancers. PROPOSED COMMERCIAL APPLICATION: There is presently no curative therapy for the treatment of low-grade follicular lymphoma in humans. This work will advance the development of a novel tumor vaccine which is showing promise in B-cell lymphoma patients. This DNA vaccine is designed to develop an anti-idiotype immune response and thereby suppress or eliminate tumor metastases. Developments in DNA technologies, such as robotic cloning and characterization of genes, will make commercial development of patient- specific vaccines feasible.

我们提出了一系列的实验，评估方法，以提高效力的质粒DNA肿瘤疫苗正在开发用于治疗低度非滤泡性淋巴瘤。基于在小鼠淋巴瘤模型系统中的临床前肿瘤攻击研究和在B细胞淋巴瘤患者中的I/II期临床试验的结果，我们已经证明了一种新的双顺反子质粒DNA载体，其设计用于在注射到肌肉组织中时引发抗独特型免疫应答，可以保护动物免受独特型肿瘤细胞攻击，并且可以在人体中产生免疫原性。最近的临床前研究表明，与单独的独特型表达质粒相比，共同注射表达鼠粒细胞-巨噬细胞集落刺激因子（mGM-CSF）的第二种DNA质粒可增加动物的免疫原性和长期保护作用。本文所述的一系列临床前实验旨在进一步提高这种多价质粒疫苗在小鼠和恒河猴中的效力。我们预计，这些实验将导致更有效的肿瘤疫苗，将在第二次临床试验中在B细胞淋巴瘤患者中进行测试。我们还预计这种治疗性疫苗的成功将导致DNA疫苗用于治疗多种人类癌症。拟议的商业应用：目前尚无治疗人类低度滤泡性淋巴瘤的治愈性疗法。这项工作将推进一种新型肿瘤疫苗的开发，这种疫苗在B细胞淋巴瘤患者中显示出希望。这种DNA疫苗旨在产生抗独特型免疫应答，从而抑制或消除肿瘤转移。DNA技术的发展，如机器人克隆和基因鉴定，将使患者特异性疫苗的商业开发成为可能。