Cytotoxic T Lymphocyte Immunotherapy for Ovarian Cancer

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DESCRIPTION: (Provided by applicant)This proposal describes a phase I clinical trial using tumor antigen specific cytotoxic T-lymphocytes (CTLs) as adoptive immunotherapy for patients with recurrent chemotherapy-resistant ovarian cancer. In this trial, subjects will undergo leukopheresis for collection of precursor lymphocytes. These precursor cells will then be stimulated and expanded in culture in the presence of MUC1, a mucin antigen specific to several malignant human cells, including ovarian cancer. The resulting CTLs will then be administered to the subject via intraperitoneal infusion. It is hypothesized that these ex-vivo generated, tumor-specific CTLs will overcome normal tumor-induced host immunosuppression and initiate effective tumor cell killing, with minimal toxicity. The specific aims of the trial are 1) to determine the toxicity and feasibility of the use of intraperitoneal infusions of tumor specific CTLs; 2) to determine the migration pattern/distribution of the CTLs by use of 111-Indium radioisotope labeling; 3) to determine if repetitive cycles of CTL generation and infusion progressively increase the measurable ovarian cancer specific activity; and 4) to observe clinical response of patients receiving MUC1-specific CTL, and if possible, correlate response to migration patterns and to the level of ovarian cancer specific activity generated by the CTLs. The longer-term goal of this trial is to serve as a basis for larger scale testing of the therapeutic effect of this technique, and ultimately to develop a new treatment modality for ovarian cancer that may be used alone or in combination with existing methods to improve outcome.