Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal

Background: Cancer-testis (CT) antigens (CTAs) have emerged as attractive targets for cancer immunotherapy. Whereas cancers of various histologies exhibit CTA expression, primary or vaccine-induced immune responses to these antigens appear uncommon in patients with these malignancies, possibly due to low-level, heterogeneous antigen expression, and inadequate vaccination strategies. Because numerous CT antigens can be induced in tumor cells by DNA demethylating agents and HDAC inhibitors, it is conceivable that vaccination of cancer patients with autologous tumor cells exposed to chromatin remodeling agents will enhance anti-tumor immunity in these individuals. In order to examine this issue, patients undergoing complete resection of sarcomas, melanomas, germ cell tumors and epithelial malignancies metastatic to the lungs, pleura or mediastinum will be vaccinated with autologous tumor cells exposed ex-vivo to decitabine and radiation following completion of appropriate combined modality therapy. Vaccines will be administered in conjunction with ISCOMATRIX adjuvant as well as metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CTAs as well as delayed type hypersensitivity to autologous epigenetically modified tumor cells will be assessed before and after vaccination. Primary Objective: -To assess the safety of an epigenetically modified autologous tumor cell vaccine administered with ISCOMATRIX adjuvant in combination with metronomic oral cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy. Eligibility: * Patients with histologically or cytologically proven or clinically evident sarcoma, melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can be rendered no evidence of disease (NED) by metastasectomy. * Patients must be 18 years or older with an ECOG performance status of 0 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences. * Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of \<1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2) at the time vaccination commences. Design: * Patients will undergo thoracic metastasectomy using standard of practice guidelines. * Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory. Cells will be processed to establish a cancer cell line. * Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation, patients will be vaccinated with epigenetically-modified autologous tumor cells periodically over 6 months in conjunction with metronomic oral cyclophosphamide and celecoxib. * Systemic toxicities and delayed type hypersensitivity responses to autologous tumor cells and serologic responses to a variety of CT antigens will be assessed before and after vaccination. * Patients will be followed with routine staging scans until disease recurrence. * As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive. * Approximately 80 patients will be accrued to this trial in order to obtain up to 20 evaluable patients.