Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor-1 alpha chemokine genes

Several new lymphocyte-specific chemokines, which attract naive and memory T cells, B cells, dendritic cells and natural killer cells, have been isola ted. We have found evidence of the anti-tumor effects of 3 major lymphocyte -specific chemokines, secondary lymphoid tissue chemokine (SLC), EBI-I-liga nd chemokine (ELC) and stromal cell-derived factor (SDF)-1 alpha, in murine models (Meth A fibrosarcoma and HM-I ovarian tumor). In both naive and imm unized mice, tumors expressing SLC, ELC or SDF-I alpha showed delayed progr ession compared with control tumors. In mice immunized with tumor cells exp ressing I of these 3 chemokine genes, challenge with parental tumor cells r esulted in slightly slower progression than in control mice, while in mice Immunized with tumor cells transfected to co-express IL-2 or granulocyte-ma crophage colony-stimulating factor (GM-CSF) as well as these chemokines, al l tumors regressed. Furthermore, spleen cells from mice immunized with thes e "double-transfected" tumor cells exhibited higher proliferative responses and greater cytotoxic activity against parental tumor cells. These anti-tu mor effects were associated with profound alterations in the leukocyte popu lations within the tumors and regional lymph nodes, and this was due to act ivation of type I T cell-dependent responses that produced high levels of I FN-gamma. These findings show that SLC, ELC and SDF-I alpha enhance anti-tu mor immunity both systemically and locally and that these chemokines may be clinically useful, especially when combined with IL-2 and GM-CSF. (C) 2001 Wiley-Liss, Inc.