title: Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.
abstract: Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic cells (DCs). Adjuvants that improve DC function and antigen cross-presentation are therefore advantageous for inducing anti-tumor immunity. Previously, we have reported that in situ tumor destruction of established murine tumors by ablation efficiently delivers antigens to DC for the in vivo induction of anti-tumor immunity. Yet, tumor ablation alone resulted in only partial protection against a subsequent tumor-challenge. In this article, the ability of various non-microbial vaccine adjuvants to modulate the immune response following cryo-ablation was tested. The data show that tumor ablation with co-injection of saponin-based adjuvants, but not oil-in-water, water-in-oil or alum-based adjuvants, creates a highly effective in situ vaccine. Draining lymph node CD11c+ DCs acquire antigens more efficiently and become increasingly activated following ablation with saponin adjuvants relative to ablation alone. Moreover, our data reveal that the saponin-based adjuvants facilitate an in this model unprecedented level of antigen cross-presentation, induction of tumor-specific CTL and long-lasting tumor protection. Collectively, combining saponin-based adjuvants with in situ tumor destruction leads to an extremely potent systemic anti-tumor response. This combination approach forms a powerful in situ DC vaccine for which no prior knowledge of tumor antigens is required. As saponin-based adjuvants are currently clinically available, they represent attractive tools for various human and veterinary settings where in situ tumor destruction is applied.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Martijn H
authors.initials: MH
authors.lastname: den Brok
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
authors.forename: Jori A
authors.initials: JA
authors.lastname: Wagenaars
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Ruers
authors.forename: Carla C
authors.initials: CC
authors.lastname: Schrier
authors.forename: Eric O
authors.initials: EO
authors.lastname: Rijke
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D003452:Cryosurgery; D003713:Dendritic Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000601:surgery*; D012503:Saponins / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D012503:Saponins