Therapeutic effects of idiotype vaccination can be enhanced by the combination of granulocyte–macrophage colony‐stimulating factor and interleukin 2 in a myeloma model

Idiotype (Id) vaccination provides an interesting immunotherapeutic strategy against B‐cell lymphomas. In multiple myeloma (MM), however, the therapeutic efficacy of Id vaccination has been disappointing. In an attempt to improve the antitumoral potential, we added granulocyte‐macrophage colony stimulating factor (GM‐CSF) and interleukin 2 (IL‐2) to the protocol. Balb/c mice were inoculated i.p. (d 2) with different doses (1–5 × 105) of HOPC myeloma cells secreting the IgHOPC Id protein. Two days later, animals were injected with 10 000 U GM‐CSF i.p. for 6 d consecutively (d 0–5). On d 5 and 11, myeloma‐specific immunoglobulin (IgHOPC) was administered i.p. together with incomplete Freund adjuvans followed by IL‐2 (2 × 10 000 U/d; i.p) for 10 d (d 5–14). In animals inoculated with 105 myeloma cells, treatment with IL‐2 given as a single agent prolonged the median survival time (MST, 67 d) when compared with the tumour control group (MST 48 d), whereas GM‐CSF did not elicit any survival benefit (MST 49 d). Complete tumour rejection could be achieved in 27% (4/15) by the combination of Id vaccination and GM‐CSF. Additional treatment with IL‐2 further increased antimyeloma activity. In this case, 59% of the animals showed no signs of tumour recurrence. In mice with high tumour burden (5 × 105), no treatment modality achieved long‐term survivors. Both natural killer (NK) cells and CD8+ T cells may be involved in the antitumoural immune response. These data provide evidence for the combined use of GM‐CSF and IL‐2 to enhance the therapeutic effectiveness of clinical cancer vaccination protocols.