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 a peptide fragment of 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 are immune type HLA-A2, 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 peptide. 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. We have completed enrollment and treatment of the patients on this study and are now following them for toxicities, immune responses, and progression-free survival. Twenty one patients were enrolled and 15 were evaluable (the remainder did not receive all the immunizations or undergo the follow-up leukpaheresis). There were no toxicities directly referable to the treatments. One patient had a minor response and one stable disease. 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 localized pancreatic cancer.
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