Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer

Background Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response. Methods We applied tumor cell lysate plus keyhole limpet bemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n = 6) or intranodally (n = 8) as a cancer vaccine to patients suffering from advancedsolid pediatric malignancies. Results No serious adverse events were observed following application of IL-12-releasing smDC Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitiviy (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test. Discussion We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.