IL-1 receptor antagonist anakinra enhances tumour growth inhibition in mice receiving peptide vaccination and beta-(1-3),(1-6)-D-glucan.

BACKGROUND

Immunotherapy of cancer by vaccination is hampered by tumour-mediated immune suppression, to which pro-inflammatory cytokines such as interleukin-1 (IL-1) and IL-6 contribute. In mouse models, IL-1-receptor antagonist (IL-1 Ra) diminished inflammation and tumour growth when administered during or shortly after tumour inoculation.

MATERIALS AND METHODS

The capacity of IL-1 Ra anakinra to reduce IL-1-induced production of IL-6 in order to improve the efficacy of a subsequent booster vaccination with survivin-derived peptides and soluble β-glucan as adjuvant was tested in colon-26 adenocarcinoma-bearing Balb/c-mice.

RESULTS

Bolus administration of anakinra into non-immunized mice with macroscopic tumour significantly lowered serum levels of IL-6 without inhibiting tumour growth. When administered to pre-immunized mice bearing a palpable tumour, IL-1 Ra enhanced growth inhibition of a subsequent booster vaccination, although serum-IL-6 was not reduced and the number of IFN-γ-producing splenic CD8(+) T-cells was not increased.

CONCLUSION

Anakinra contributes to growth-inhibition of small tumours, presumably by blocking IL-1 as tumour growth-promoting factor rather than by facilitating an enhanced CTL response.