Immunization with fowlpox vector-modified dendritic cell in patients with carcinoembryonic antigen-expressing cancer: Phase I clinical study
A dendritic cell (DC), which can induce a primary immune response, is known to be the most potent antigen-presenting cell in the immune system. Many studies have been performed to evaluate the safety and efficacy of DC-based immunotherapy. At Duke University Medical Center, various methods of tumor antigen-loading to DC (i.e., peptide, protein, mRNA, virus vectors) were tried in patients with carcinoembryonic antigen (CEA)-expressing colorectal/lung cancers, HER2-expressing breast cancers, or prostate specific antigen (PSA)-expressing prostate cancers. In this article, we report the results of our latest study, a phase I clinical study of immunization with DCs modified with fowlpox vector encoding carcinoembryonic antigen and costimulatory molecules. We administered one or two cycles of four triweekly subcutaneous/intradermal injections of CEA-expressing DCs. Among the 14 patients enrolled (11 with colorectal cancer, 3 with non-small cell lung cancer), 12 patients completed at least one cycle of immunization. There were no immunization-related grade 3/4 toxicities. One patient showed a decrease in the CEA level and regression of the lymphadenopathy that occurred several months after completion of immunization. Five other patients were stable through at least one cycle of immunization. Immune monitoring assays showed induction of CEA-specific immune response in all immune responders. Thus, this vaccine strategy is safe, induces potent CEA-specific immune responses, and warrants further study.
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