LL-37 enhances adaptive antitumor immune response in a murine model when genetically fused with M-CSFRJ6-1 DNA vaccine

Abstract: DNA vaccine against M-CSFRJ6-1 (macrophage colony-stimulating factor receptor cloned from the J6-1 leukemic cell line) has shown both protective and therapeutic effects. In this study, to explore the adjuvant effects of LL-37 to M-CSFRJ6-1 DNA vaccines, we constructed genetically fused vaccines encoding M-CSFRJ6-1 and LL-37(pF). After immunizing BALB/c mice, specific humoral and cellular immune responses were detected. Compared with pR (encoding the extracellular region of M-CSFRJ6-1), pF was more effective in inducing humoral and cytotoxic immune response, prolonging survival of mice challenged with SP2/0-CSFRJ6-1 tumor cells, and inducing IFN-γ and IL-4 release by splenocytes. In this study, we also constructed pLL37 (encoding the mature LL-37) and coadministrated pLL37 and pR to see whether the genetic fusion was necessary. We found that compared with pR alone, pLL37+pR could not prolong survival of mice challenged with SP2/0-CSFRJ6-1 tumor cells. Our results suggest that when genetically fused with M-CSFRJ6-1, LL-37 could enhance adaptive immune response against M-CSFRJ6-1 in a murine model challenged with tumor cells bearing M-CSFRJ6-1. [Copyright &y& Elsevier]