Background: Cellular immunotherapy with DC is a feasible strategy with proved activity in the treatment of cancer. Preclinical and clinical data indicate that efficacy of DC immunotherapy is improved when used in clinical settings of minimal residual disease, and Sipuleucel-T is the first approved treatment based in this approach. We are exploring the efficacy of an autologous vaccine of DC loaded with self-tumor antigens that we developed in a previous pilot trial (Alfaro, J Immunology 2011) in patients with colorectal cancer with completely resected hepatic metastasis following standard adjuvant treatment. Methods: In this randomized phase II study, patients with colorectal carcinoma with hepatic metastasis treated with complete surgical resection and standard adjuvant chemotherapy are randomized to receive DC vaccine or observation. The two-cycle vaccination protocol includes the following strategies: (1) pretreatment with cyclophosphamide to decrease regulatory T cells; (2) maturation and activation of DC with TNF-alpha, interferon-alpha and poly I:C, a potent inducer of type I interferon; (3) use of autologous tumor from resected liver metastasis as antigenic source to load antigens onto DC, including antigens that are exclusive of tumor cells; and (4) administration of daily intradermal vaccines during four consecutive days in 2 cycles every 4 weeks. The strategy is to replicate the immune response induced during an acute viral infection in terms of activation signals and persistence of antigens in lymph nodes. The main objective is progression-free survival. Thirty-six patients will be included, allowing to detect a HR=1.75 (alpha error=0.2, beta error=0.35). Secondary objectives include assessment of toxicity, overall survival and immunologic response (in vitro lymphocyte responses against tumor antigens; delayed hypersensitivity reactions; induction of tumor antibody responses; DC activation parameters including IL-12 and IL-6 production and expression of CD80, CD83, CD86, B7-H1, B7-H4 and B7-DC; assessment of DC maturation by expression of pro-inflammatory cytokines; and DC migration). Clinical trial information: NCT01348256.