Therapeutic effect of MIP-1α-recruited dendritic cells on preestablished solid and metastatic tumors

Abstract 

We previously found that dendritic cell (DC) precursors could be recruited into the peripheral blood of B6 mice by administration of macrophage inflammatory protein (MIP)-1α. These MIP-1α-recruited DCs could induce anti-tumor protective immunity when pulsed with tumor cell lysate. In this study, MIP-1α-recruited DCs could not effectively suppress preestablished tumor when pulsed with B16 tumor cell lysate. However, inoculation with these DCs expressing MAGE-1 induced an anti-tumor immunity against preestablished solid and metastatic tumor from B16-MAGE-1 cells. These MIP-1α-recruited DCs expressed higher level of CCR7 and displayed a more significant chemotactic response toward secondary lymphoid tissue. Therefore, they are superior in the induction of cytotoxic T lymphocytes and the inhibition of tumor development and metastasis than bone marrow-derived DCs. This study established a novel approach to the treatment of preestablished solid and metastatic tumors using MIP-1α-recruited DCs transduced with tumor antigen gene.

Abbreviations: B16-MAGE-1, B16F10 cells transduced with a retrovirus encoding the human MAGE-1 gene, Ad-MAGE-1, recombinant adenovirus expressing MAGE-1 gene, MIP-1α-DC-TP, MIP-1α-recruited DC pulsed with tumor lysate of B16 cells, BM-DC-TP, bone marrow-derived DC pulsed with tumor lysate of B16 cells, MIP-1α-DC-Ad-MAGE-1, MIP-1α-recruited DC transduced with MAGE-1 gene, BM-DC-Ad-MAGE-1, bone marrow-derived DC transduced with MAGE-1 gene, MIP-1α-DC-TP-MAGE-1, MIP-1α-recruited DC pulsed with tumor lysate of B16-MAGE-1 cells, BM-DC-TP-MAGE-1, bone marrow-derived DC pulsed with tumor lysate of B16-MAGE-1 cells

Keywords: Cancer, Immunotherapy, Dendritic cells