Background: To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy,\nwe conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen\n(CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in\nthe vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine\nefficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of\nvaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment.\nMethods: Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic\ncolorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic\ncolorectal cancer with 1 Ã?â?? 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive\ninjections with 1 Ã?â?? 106 CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the\nfinal DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical\nstatus. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation\nresponses against CEA.\nResults: No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC\nvaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically\nsignificant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients.\nConclusions: The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this\nprotocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of\npatients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications\nto enhance T cell responses.
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