LL-37 enhances adaptive antitumor immune response in a murine model when genetically fused with M-CSFR (J6-1) DNA vaccine.
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).
An
Li-Li
LL
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.
Yang
Ying-Hua
YH
Ma
Xiao-Tong
XT
Lin
Yong-Min
YM
Li
Ge
G
Song
Yu-Hua
YH
Wu
Ke-Fu
KF
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
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