title: Hyper-interleukin-11 novel designer molecular adjuvant targeting gp130 for whole cell cancer vaccines.
abstract: BACKGROUND
  Hyper-IL-11 (H11) is a fusion protein comprising IL-11 and soluble IL-11 receptor directly targeting gp130. We evaluated efficacy of H11 as a molecular adjuvant in therapeutic whole tumor cell vaccine formulation.
  
  
  METHODS
  H11 was tested in ectopic and orthotopic murine renal cell carcinoma (RENCA) models. H11 cDNA was transduced into RENCA cells (RENCA-H11). Mice were immunized with RENCA-H11 or control vaccine (RENCA-IRR) in prophylactic, adjuvant and therapeutic settings. Tumor formation, survival and immune mechanisms activated by H11 were studied.
  
  
  RESULTS
  Biologically active H11 was secreted by RENCA-H11 cells. Immunization with RENCA-H11 resulted in mounting specific anti-RENCA response. Treatment of tumor bearing mice in adjuvant setting prevented disease recurrence in therapeutic setting eradicated tumors. In induction phase H11 inhibited T-regulatory cell formation and activated recruitment and maturation of dendritic cells. Downstream of immunization tumors were densely infiltrated by CD8(+), CD4(+), NK cells, cells expressing CD8(+)CD69(+) and CD4(+)CD62L(low).
  
  
  CONCLUSIONS
  H11 is a good candidate for adjuvant of whole tumor cell vaccines. Direct targeting of gp130 leads to induction of specific and long lasting anticancer immune response. Enhancement of tumor antigen presentation, abrogation of immune tolerance, and activation of NK cells and generation of memory cells lead to eradication of existing tumors.
authors: University of Medical Science, Medical Biotechnology, Garbary 15, Poznan, 61 866, Poland.
authors: Wiktoria Maria
authors: WM
authors: Suchorska
authors: Hanna
authors: H
authors: Dams-Kozlowska
authors: Urszula
authors: U
authors: Kazimierczak
authors: Piotr Jan
authors: PJ
authors: Wysocki
authors: Andrzej
authors: A
authors: Mackiewicz
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D017370:Interleukin-11 / Q000235:genetics / Q000276:immunology*; D053703:Interleukin-11 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014161:Transduction, Genetic; D047368:Tumor Burden
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C508611:IL11 protein, human; C508428:IL11RA protein, human; C494200:Il6st protein, mouse; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130