Inter-alpha Inhibitors in Detecting CNS Cancer

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DESCRIPTION (provided by applicant) The overall goal is to develop a marketable novel predictive marker based on inter-alpha inhibitor proteins (laIp) in cerebrospinal fluid (CSF) that can be utilized in the management of CNS cancer. Cost effective care, successful palliation of symptoms and new therapeutic insights for patients with primary and metastatic CNS cancer as well as with the involvement of leptomeninges depend largely on reliable diagnostic tests and outcome measures. Modem neuroimaging is useful in early diagnosis and subsequent monitoring of patients with CNS cancer. However, these studies are expensive and are limited by false negative and false positive findings. CSF cytology is the "gold standard' diagnosis for leptomeningeal carcinomatosis. Unfortunately, false-negative results are very common. Currently, there are no biochemical markers that can detect the presence or activity of primary and metastatic CNS cancer. In our preliminary studies, when the CSF of CNS cancer patients were analyzed by Westernblot with a monoclonal antibody specific against human laIp, the levels of lalp were greatly elevated relative to those from non-cancer control patients or from systemic cancers without demonstrable CNS disease. The levels of IaIp suggest correlation with tumor burden and disease progression as well as response to therapy, raising the potential of lalp as a sensitive indicator. The detection of laIp in CSF seems to be a more accurate predictor of the presence of tumor cells in the CSF than conventional CSF cytology. In this proposal, we will focus on the development of a sensitive quantitative assay and a rapid semi quantitative immunoassay format that can be used without instrumentation. We will determine whether measurement of lalp levels in CSF allows for early detection and subsequent monitoring of primary and metastatic CNS malignancies and whether CSF IaIp levels facilitate an accurate prediction of treatment response and survival.