Immunotherapy has emerged as a promising strategy to eradicate cancer cells. Particularly, the development of cancer vaccines to induce a potent and sustained antigen-specific T cell response has become a center of attention. Herein, we describe a novel immunotherapy based on magnetic nanoparticles (MNP) covalently modified with the OVA antigen and a CpG oligonucleotide disulfide bonds. The MNP-CpG-COVA significantly enhances dendritic cell activation and CD8 T cell antitumoral response against B16-OVA melanoma cells . Notably, the immune response induced by the covalently modified MNP is more potent and sustained over time than that triggered by the free components, highlighting the advantage of nanoformulations in immunotherapies. What is more, the nanoparticles are stable in the blood after administration and induce potent levels of systemic tumor-specific effector CD8 + T cells. Overall, our findings highlight the potential of covalently functionalized MNP to induce robust immune responses against mouse melanoma.