TUMOR IMMUNOTHERAPY

肿瘤免疫治疗

• 批准号: 3506788
• 负责人: PHILLIP R MORROW
• 金额: $ 20.94万
• 依托单位: AVANIR PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3506788
• 关键词: antineoplastics; biomaterial development /preparation; cell mediated lymphocytolysis test; cellular immunity; clone cells; combination chemotherapy; cytotoxic T lymphocyte; disease /disorder model; dosage; drug design /synthesis /production; drug screening /evaluation; immunopharmacology; immunotoxicity; laboratory mouse; leukocyte activation /transformation; lymphokines; melanoma; neoplasm /cancer immunotherapy; neoplastic growth; nonhuman therapy evaluation; protein purification; tumor antigens

A novel form of tumor antigen, termed Large Multivalent Immunogen (LMI), has been found to enhance in vivo tumor-specific cytolytic responses, and to significantly reduce tumor growth and extend survival of tumor-bearing animals. LMI are prepared by isolating tumor cell surface membranes and immobilizing these on cell-size microspheres. Work done under Phase I of this project has established the novel ability of LMI to mediate tumor reduction, in comparison to other forms of antigen, and demonstrated that treatment of mice bearing established, progressing P815 (mastocytoma) solid tumor with a combination of cyclophosphamide and LMI results in long term survival of the majority of the mice. Phase II of this project has two major goals; to study the mechanism(s) by which LMI treatment reduces tumor growth, and to develop LMI technology for use in humans and obtain data needed to initiate clinical trials. This will include development of a non-toxic, biodegradable support material for preparation of LMI, and in vitro studies of LMI-mediated activation of cloned human cytolytic T lymphocytes (CTL) specific for melanoma antigens. We anticipate being able to initiate a clinical trial with melanoma patients by the end of this Phase II project, and possibly sooner.

一种新形式的肿瘤抗原，称为大多价免疫原（LMI）， 已发现增强体内肿瘤特异性细胞溶解反应， 以显著减少肿瘤生长并延长荷瘤患者的生存期， 动物 通过分离肿瘤细胞表面膜制备LMI， 将它们固定在细胞大小的微球上。 第一阶段完成的工作 该项目已经建立了LMI介导肿瘤的新能力， 减少，与其他形式的抗原相比，并证明， 治疗已建立的、进展中的P815（肥大细胞瘤）实体瘤小鼠 环磷酰胺和LMI联合治疗肿瘤的长期结果 大多数老鼠的生存。 该项目的第二阶段有两个主要目标：研究机制， LMI治疗减少肿瘤生长，并开发LMI技术， 用于人体并获得启动临床试验所需的数据。 这 将包括开发一种无毒、可生物降解的支持材料， LMI的制备，以及LMI介导的活化的体外研究。 克隆的对黑色素瘤抗原特异的人细胞溶解性T淋巴细胞（CTL）。 我们希望能够启动一项针对黑色素瘤的临床试验 在第二阶段项目结束前，甚至可能更早。