BLADDER CANCER TUMOR ASSOCIATED ANTIGENS

膀胱癌肿瘤存在的血清学和细胞毒性证据 相关抗原已有报道。然而，这些产品的分布 抗原及其临床相关性仍有待确定。这个 这项提议的目标是准确地定义存在， 肿瘤相关抗原的分布及其临床意义 膀胱癌细胞。这将使用以下方法来完成 方法： 1.建立新的膀胱癌组织培养细胞系。 这些细胞系将作为后续的抗原源。 分析。 2.患者血清与组织中肿瘤细胞的自体结合 培养将通过免疫黏附和蛋白A分析进行测试 确定细胞表面肿瘤是否存在自体反应性 相关抗原。自体检测消除了由 同种异体组织，并允许识别独有的抗原 个别肿瘤。高滴度血清将进一步进行血清学分析 利用各种正常和恶性细胞系吸收 定义反应性的分布。两者之间的相关性 自身抗体的存在和患者的临床病程 评估是否存在自体肿瘤抗体 会改变病人的预后。 3.将产生针对膀胱癌的鼠源性单抗 使用新的和先前确定的膀胱癌的相关抗原 细胞系。混合血吸附法的血清学特征 将用来定义单抗反应性的分布 培养细胞上的抗体。此外，还将在以下方面进行测试 福尔马林固定和冰冻组织切片用免疫过氧化物酶分析。 分布有限的单抗将被用于定义 人类膀胱癌的亚型。由细胞表面抗原定义的肿瘤 表型将与患者的临床病程相关 携带这些肿瘤以确定功能不同的肿瘤，即， 具有不同预后的肿瘤可以被识别。

Serologic and cytotoxic evidence for the existence of bladder cancer tumor associated antigens have been reported. However, the distribution of these antigens and their clinical relevance remains to be defined. The objectives of this proposal are to accurately define the existence, distribution, and clinical relevance of tumor associated antigens on bladder cancer cells. This will be accomplished using the following methods: 1. New bladder carcinoma cell lines will be established in tissue culture. These cell lines will serve as a continual source of antigen for subsequent analysis. 2. Autologous combinations of patient's sera and tumor cells in tissue culture will be tested using the immune adherence and protein A assays to determine the presence of autologous reactivity to cell surface tumor associated antigens. Autologous testing eliminates reactivity caused by allogantigens and permits identification of antigens unique for an individual tumor. High titer sera will be further analyzed with serologic absorption using a wide variety of normal and malignant cell lines to define the distribution of the reactivity. Correlation between the presence of autologous antibody and the patient's clinical course will be assessed to evaluate whether the presence of antibody to autologous tumor alters the patient's prognosis. 3. Murine monoclonal antibodies will be produced to bladder tumor associated antigens using new and previously established bladder cancer cell lines. Serologic characterization with the mixed hemadsorption assay will be used to define the distribution of reactivity of the monoclonal antibodies on cultured cells. In addition, testing will be performed on formalin fixed and frozen tissue sections using an immunoperoxidase assay. Monoclonal antibodies with limited distribution will be used to defined subsets of human bladder cancer. Tumors defined by cell surface antigen phenotype will then be correlated with the clinical course of patient's bearing these neoplasms to determine if functionally different tumors, ie., neoplasms with different prognoses, can be identified.