title: 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).
authors.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.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: An
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Ma
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Song
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Wu
mesh_terms: D000222:Adaptation, Physiological; D000276:Adjuvants, Immunologic; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D019556:COS Cells; D002633:Chemotaxis; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007107:Immune System / Q000502:physiology*; D007114:Immunization; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*; D054804:Cathelicidins
chemical_list: D000276:Adjuvants, Immunologic; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D016186:Receptor, Macrophage Colony-Stimulating Factor; D054804:Cathelicidins