Dendritic-tumor cell hybrids in therapeutic vaccination against advanced neuroblastoma

Abstract

Neuroblastoma is a common intra-abdominal tumor in children that may have an aggressive behavior and poor response to therapy, needing, therefore, new therapies. Monocyte-derived dendritic cells (Mo-DCs) can be applied in the development of immunotherapy against cancer, but in cancer patients present phenotypic and functional changes that impair their potential to induce effective responses. To circumvent this, Mo-DCs from healthy donors can be fused to patients’ tumor cells and, after irradiation, used to initiate anti-tumor responses. Fused cells maintain the expression of both tumor and Mo-DC markers. Furthermore, the heterokaryons seem to survive and proliferate better than non-fused cells (both tumor and DCs) in culture. When fused cells were utilized to stimulate patients’ lymphocytes, they were able to induce the production of a distinct cytokine pattern, characterized by a higher IFN-gamma and a lower IL-4 production. We report further, the preliminary results of a protocol using this vaccination strategy in patients with histological diagnosis of neuroblastoma. Tumor samples from 63 patients were obtained, processed into single cell suspensions and stored for later use. Seventeen patients already received the vaccination, nine patients after autologous bone marrow transplantation (as included in the Brazilian neuroblastoma treatment protocol NEURO-X-2008). Clinical responses ranged from complete clinical remission to none. The average number of monthly doses received is 3.3 (one dose/month) and no significant adverse side effects were noted. Thus, the further characterization of the responses induced by this treatment could establish this approach as an effective treatment modality for patients with neuroblastoma.