Establishment of cancer immunotherapy with autologous dendritic cells and tumor-specific antigens in children with refractory malignant tumors

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Purpose : Immunotherapy has recently emerged as a promising new modality in cancer therapy. In this study. autologous dendritic cells (DCs) pulsed with tumor specific antigens in vitro were administered to patients and induced cytotoxic T cells (CTLs) against tumor cells Is in order to cure children with refractory cancers.Materials and Methods : DCs were generated from patients' peripheral blood mononuclear cells by using hrGM-CSF and hrIL-4. The generated immature DCs were pulsed with tumor specific antigens (synthetic peptides containing a junctional region of the chromosomal translocation specific to tumor cells or tumor lysates), and injected to patients subcutaneously at a dose of 3×10^6 cells. The administration was repeated weekly or biweekly 6 to 8 times.Results : Five patients with refractory or relapsed diseases (Ewing sarcoma (ES) 1. synovial sarcoma (SS) 1. neuroblastoma (NB)3) received DC therapy. No side effects were observed after DC administration. In one patient with ES. the residual tumor disappeared following DC therapy and the complete remission has been maintained for over 2 years. In two patients (55 and NB). the growth of the tumors was temporal ly suppressed for a couple of weeks, followed by the rapid exacerbation. No clinical improvement was observed in other two. In the patient with SS, the delayed-type hypersensitivity responses in skin were enhanced to tumor lysates, and T cells cultured with DCs pulsed with tumor specific antigens destroyed the tumor cells in vitro. The number of HLA-DR+ CD8+ cells and IFN-γ producing CD8+ cells increased after DC administration in patients with possible DC-mediated anti-tumor effect.Conclusions : DC-based immunotherapy was a feasible. well-tolerated and promising approach in the treatment of children with refractory malignant tumors.