부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.leukres.2004.11.009 Byline: Li-Li An, Ying-Hua Yang, Xiao-Tong Ma, Yong-Min Lin, Ge Li, Yu-Hua Song, Ke-Fu Wu Keywords: LL-37; Macrophage colony-stimulating factor receptor; Antitumor activities; Adaptive immunity Abbreviations: hCAP-18, human cationic antimicrobial protein 18; LL-37the C-terminal, active biologic domain of hCAP-18; M-CSFR.sub.J6-1, macrophage colony-stimulating factor receptor (M-CSFR) cloned from the J6-1 leukemic cell line; mM-CSF, membrane-bound macrophage colony-stimulating factor; FCS, fetal calf serum; PVDF, polyvinylidene difluoride; IL, interleukin; BSA, bovine serum albumin; IFN, interferon; AML, acute myeloid leukemia; PCR, polymerase chain reactions; ABC complex, avidin-biotin-peroxidase complex; NS, normal saline; CTL, cytotoxic T lymphocyte; E:T ratio, the ratio of effectors and target cells; DCs, dendritic cells; PTK, protein tyrosine kinase; APCs, antigen-presenting cells; mDF2[beta], murine [beta]-defensin2; TLR-4, toll-like receptor 4 Abstract: DNA vaccine against M-CSFR.sub.J6-1 (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-CSFR.sub.J6-1 DNA vaccines, we constructed genetically fused vaccines encoding M-CSFR.sub.J6-1 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-CSFR.sub.J6-1), pF was more effective in inducing humoral and cytotoxic immune response, prolonging survival of mice challenged with SP2/0-CSFR.sub.J6-1 tumor cells, and inducing IFN-[gamma] 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-CSFR.sub.J6-1 tumor cells. Our results suggest that when genetically fused with M-CSFR.sub.J6-1, LL-37 could enhance adaptive immune response against M-CSFR.sub.J6-1 in a murine model challenged with tumor cells bearing M-CSFR.sub.J6-1. Author Affiliation: National Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China Article History: Received 2 March 2004; Accepted 3 November 2004