Enhanced antitumoral effectiveness of idiotype vaccination induced by the administration of Flt3 ligand combined with interleukin 2 against a murine myeloma.

Abstract

Idiotype (Id) vaccination provides an innovative treatment modality against B-cell malignancies. In multiple myeloma patients, however, the antitumoral potential of this immunotherapeutic concept is limited. In an attempt to improve the therapeutic effectiveness of Id vaccination, we added Flt3 ligand (Flt3-L) and interleukin 2 (IL-2) to the protocol. Balb/c mice were inoculated i.p. (d -2) with different doses (1-5 x 10(5)) of HOPC myeloma cells, secreting the IgHOPC Id-protein. Two days later, animals were treated with Flt3-L (10 microg per mouse/d, given i.p) for 10 consecutive days (d 0-9). On d 5 and d 11, myeloma-specific immunoglobulin (Ig(HOPC)) was administered s.c., together with incomplete Freund adjuvans (IFA) followed by the administration of IL-2 (2 x 10.000/d given i.p) for 10 d (d 5-14). Whereas Ig(HOPC), Flt3-L or IL-2, given alone, did not elicit long-term survival, the combination of IL-2 or Flt3-L with Id vaccination achieved a complete tumour rejection in 27% and 41% of mice respectively. However, the most powerful antimyeloma effects were induced by Flt3-L + Id vaccination + IL-2: 81% of the treated animals experienced long-term survival (> 180 d). Both natural killer (NK) cells and CD8+ T cells may be involved in the antitumoral immune response. These data suggest that the combination of Flt3-L and IL-2 can be used to enhance the therapeutic effectiveness of clinical cancer vaccination protocols.