Because metastatic solid organ tumors are often incurable with standard approaches, other strategies such as inducing immune responses against the tumor are being explored. The purpose of this study is to evaluate the safety and feasibility of one such form of immunotherapy, vaccinations with potent immune stimulating cells called dendritic cells (DC) loaded with the RNA encoding a tumor-associated protein, carcinoembryonic antigen (CEA) for patients with metastatic CEA expressing malignancies such as gastrointestinal, lung, and breast cancers. Patients are screened to assure that they have a tumor that expresses CEA, and have advanced or metastatic disease that has failed conventional therapy. Eligible patients are leukapheresed, their peripheral blood mononuclear cells are cultured with GM-CSF and IL-4 to produce DC, and the DC are mixed with CEA RNA. Patients are assigned to the appropriate dose levels and receive intravenous and intradermal injections of the dendritic cells on day one of weeks 0, 2, 4, and 6. A repeat leukapheresis is performed at the end of the immunizations to determine the immune response induced against CEA. The goal was to enroll 18 evaluable patients, defined as those who received all immunizations and underwent the final leukpaheresis. (Over accrual was allowed if patients began the study before the 18th completed their treatment). Subsequently we amended the protocol to allow a further accrual of 18 patients who would receive total tumor RNA (containing CEA)-loaded DC if tumor tissue was available. We have completed enrollment and treatment of the patients receiving CEA RNA loaded DC on this study and are now following them for toxicities, immune responses, and progression-free survival. Thirty one patients were enrolled and 22 were evaluable (the remainder did not receive all the immunizations or undergo the follow-up leukpaheresis). We have enrolled one patient on the total tumor RNA protocol. There were no toxicities directly referable to the treatments. Two patients had a minor response and five were stable. The immunologic response data is being analyzed presently. This study is significant in that it demonstrates the safety and feasibility of this approach and provides the groundwork for phase II studies of the immunologic efficacy of these vaccines. We plan to focus on settings of minimal residual disease for the phase II studies, including after resection of hepatic metastases of colon cancer.
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