In vitro adaptation of a murine colorectal cell line (MoCR) rendered it less aggressive and more immunogenic than the in vivo passaged parent tumor. Vaccination of syngeneic mice with the in vitro cultured tumor cells was shown to induce immune responses and protection against tumor challenge, thus overcoming the need for antigen selection and adjuvants. A syngeneic murine model of colorectal cancer (CRC) liver metastasis was used. In a prophylactic setting mice vaccinated with in vitro cultured tumor cells produced strong cellular immune responses and significant inhibition of tumor growth, compared to sham vaccinated controls. In a therapeutic setting however, vaccination exacerbated tumor growth, suggesting that the presence of tumor subverts the course of the immune response. The mechanisms of this subversion need to be investigated and counteracted for successful immunotherapy.