TUMOR IMMUNOTHERAPY

一种新形式的肿瘤抗原，称为大分子多价免疫原(LMI)， 已被发现可增强体内肿瘤特异性细胞溶解反应，以及 显著抑制肿瘤生长，延长荷瘤小鼠生存期 动物。LMI通过分离肿瘤细胞表面膜和 将它们固定在细胞大小的微球上。根据第I阶段完成的工作 这个项目已经建立了LMI介导肿瘤的新能力 减少，与其他形式的抗原相比，并证明 P815(肥大细胞瘤)实体瘤小鼠的治疗 环磷酰胺和LMI联合治疗的肿瘤长期疗效 大多数小鼠存活下来。 这个项目的第二阶段有两个主要目标；通过以下方式研究机制(S) 哪种LMI治疗可以减少肿瘤生长，并开发LMI技术用于 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的制备及体外激活LMI的研究 克隆针对黑色素瘤抗原的人细胞溶解T淋巴细胞(CTL)。 我们期望能够启动黑色素瘤的临床试验。 在这个第二阶段项目结束之前，甚至可能更早。

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.