Vaccination with IFN-inducible T cell alpha chemoattractant (ITAC) gene-modified tumor cell attenuates disseminated metastases of circulating tumor cells.

Immunotherapeutic strategies for metastatic diseases are being developed. IFN-inducible T cell alpha chemoattractant (ITAC) has been demonstrated to be able to induce Th1-type immune response. However, the effects of ITAC on the tumor metastasis have not been fully understood. In the present study, the ITAC-modified tumor cell vaccine in inhibiting the disseminated pulmonary metastasis was evaluated. ITAC-modified tumor cell vaccine 4T1-ITAC was developed by stably transfecting 4T1 cells with pcDNA3-ITAC plasmid. Mice were vaccinated with 4T1-ITAC. Mice vaccinated with 4T1-pcDNA3 and 4T1 were used as controls. Specific cellular immune responses against 4T1 were tested by in vitro proliferation, cytokine production and cytotoxic assay. The number of clonogenic metastatic tumor cells and metastatic forci on the surface of lung were counted by histological examination. Results showed that a significant enhancement of proliferative and cytotoxic activities accompanied with increased IFN-gamma and TNF-alpha production as well as decreased IL-4 production were obtained from the mice vaccinated with 4T1-ITAC. The number of clonogenic metastatic tumor cells in the mice vaccinated with 4T1-ITAC cells reduced markedly and no visible metastasis was found in the lungs of the 4T1-ITAC vaccinated mice. Consequently, the survival rate was dramatically increased in these mice. Taken together, our results demonstrated that ITAC-modified tumor cell vaccine can enhance the anti-tumor immunity and reduce the incidence of disseminated metastasis.