Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction

Martijn H. Den Brok, Stefan Nierkens, Jori A. Wagenaars, Theo J. Ruers, Carla C. Schrier, Eric O. Rijke, Gosse J. Adema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

32 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)737-744
Aantal pagina's8
TijdschriftVaccine
Volume30
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 17 jan. 2012
Extern gepubliceerdJa

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