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LL-37 enhances adaptive antitumor immune response in a murine model when genetically fused with M-CSFR (J6-1) DNA vaccine.

Abstract
DNA vaccine against M-CSFR(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(J6-1) DNA vaccines, we constructed genetically fused vaccines encoding M-CSFR(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(J6-1)), pF was more effective in inducing humoral and cytotoxic immune response, prolonging survival of mice challenged with SP2/0-CSFR(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(J6-1) tumor cells. Our results suggest that when genetically fused with M-CSFR(J6-1), LL-37 could enhance adaptive immune response against M-CSFR(J6-1) in a murine model challenged with tumor cells bearing M-CSFR(J6-1).
AuthorsLi-Li An, Ying-Hua Yang, Xiao-Tong Ma, Yong-Min Lin, Ge Li, Yu-Hua Song, Ke-Fu Wu
JournalLeukemia research (Leuk Res) Vol. 29 Issue 5 Pg. 535-43 (May 2005) ISSN: 0145-2126 [Print] England
PMID15755506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adjuvants, Immunologic
  • Antimicrobial Cationic Peptides
  • Cytokines
  • Lipopolysaccharides
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Receptor, Macrophage Colony-Stimulating Factor
  • Cathelicidins
Topics
  • Adaptation, Physiological
  • Adjuvants, Immunologic
  • Animals
  • Antimicrobial Cationic Peptides (genetics)
  • COS Cells
  • Chemotaxis
  • Chlorocebus aethiops
  • Cytokines (metabolism)
  • Female
  • Immune System (physiology)
  • Immunization
  • Leukemia (immunology, metabolism, therapy)
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Receptor, Macrophage Colony-Stimulating Factor (genetics)
  • Recombinant Fusion Proteins (genetics)
  • Survival Rate
  • T-Lymphocytes, Cytotoxic (immunology)
  • Vaccines, DNA (therapeutic use)
  • Cathelicidins

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