PRECLINICAL ANTI-IDIOTYPE THERAPY OF CANCER

在这个新的申请中，我们继续支持我们的研究， 治疗性独特型疫苗，我们专注于改善治疗性独特型疫苗， 在肿瘤治疗中的功效。 我们将采用新的组合， 化疗和抗独特型刺激以及使用过继 识别调节独特型的Th细胞的转移。 既然我们有 以前观察到，只有一个几个所谓的内部图像反- 独特型（Ab 2 β）可以防止肿瘤生长，我们将开发独特型 用于预测治疗效果和选择治疗方案的筛选方法 最好的抗独特型抗体 该计划概述了四个主要方面 具体目标： 首先，我们将分析与肿瘤相关的表达独特位- 在纵向研究中对接受抗- 独特型疗法 初步数据表明， 血清中的某些独特基因与肿瘤和疾病存活率相关 并且这些独特基因座是肿瘤生长过程的预后。 第二，我们将抑制与肿瘤相关的预后独特基因座， 并刺激那些在肿瘤存活小鼠中高的细胞 挑战. 第三，我们将继续我们的观察，即肿瘤宿主的生存可以是 使用抗独特型和 环磷酰胺 第四，我们将使用我们实验室最近建立的T辅助细胞克隆， 对抗独特型抗体的反应是增殖。 小鼠建立 肿瘤将接受独特型特异性克隆T细胞，这些T细胞将 用抗独特型进行体内刺激。 更好地了解 在过继性T辅助细胞治疗中的潜在机制，我们将研究T- 体外B协作。 最终，过继性T细胞疗法将成为 联合化疗 这些在明确定义的动物肿瘤模型中提出的实验是 有必要制定一个合理的抗独特型治疗方法， 癌症患者。

In this new application for continued support for our studies on therapeutic idiotype vaccines we focus on improving the therapeutic efficacies in tumor therapies. We will employ new combinations of chemotherapy and anti-idiotype stimulations as well as the use of adoptive transfers of Th cells recognizing regulatory idiotypes. Since we have previously observed that only one of several so-called internal image anti- idiotypes (Ab2beta) protects against tumor growth, we will develop idiotype screening methods for predicting therapeutic effects and for choosing the best anti-idiotype for therapy. This program is outlined in four major specific aims: First, we will analyze the expression idiotopes associated with the tumor- network in longitudinal studies on individual tumor mice undergoing anti- idiotype therapy. Preliminary data indicated that the expression of certain idiotopes in serum is correlated with tumor and disease survival and that these idiotopes are prognostic for the course of the tumor growth. Second, we will suppress prognostic idiotopes associated with tumor progression and stimulate those which are high in mice surviving the tumor challenge. Third, we will follow up on our observation that tumor host survival can be significantly improved with combination therapy using anti-idiotype and cyclophosphamide. Fourth, we will use T helper cell clones, recently established in our lab, which respond to anti-idiotypes with proliferation. Mice with established tumors will receive idiotype-specific cloned T cells and these T cells will be in vivo stimulated with anti-idiotype. To better understand the underlying mechanism in adoptive T helper cell therapy we will study the T- B collaboration in vitro. Eventually, adoptive T cell therapy will be combined with chemotherapy. These proposed experiments in a well defined animal tumor model are necessary to develop a rational approach for anti-idiotype therapy in cancer patients.