PRECLINICAL ANTI-IDIOTYPE THERAPY OF CANCER

在此新申请继续支持我们的研究 治疗性独特型疫苗我们专注于提高治疗性 在肿瘤治疗中的疗效。我们将采用新的组合 化疗和抗独特型刺激以及过继疗法的使用 识别调节独特型的Th细胞的转移。因为我们有 之前观察到的几个所谓的内部图像中只有一个是反 独特型(Ab2beta)可防止肿瘤生长，我们将开发独特型 预测疗效和选择治疗方案的筛选方法 治疗的最佳抗独特型药物。这项计划主要分为四个部分 具体目标： 首先，我们将分析与肿瘤相关的表达独特位- 网络在个体肿瘤小鼠抗肿瘤治疗中的纵向研究 独特型疗法。初步数据显示， 血清中某些独特位与肿瘤和疾病存活期相关 这些独特异体可以预测肿瘤的生长过程。 第二，我们将抑制与肿瘤相关的预后独特异体 在存活肿瘤的小鼠中进行和刺激高表达的细胞 挑战。 第三，我们将跟进我们的观察，即肿瘤宿主的存活率可以 使用抗独特型和联合治疗显著改善 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， 它们对增殖的抗独特型有反应。已建立的小鼠 肿瘤将接受独特型特异性克隆T细胞，这些T细胞将 在体内用抗独特型刺激。为了更好地理解 采用辅助性T细胞治疗的潜在机制我们将研究T- B体外协作。最终，采用T细胞疗法将是 再加上化疗。 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.