Murine renal cell carcinoma: evaluation of a dendritic‐cell tumour vaccine

Abstract

OBJECTIVE: To use a murine model of renal cell carcinoma (RCC), Renca, to aid in developing a dendritic cell (DC)-mediated tumour vaccine for RCC; as conventional therapy has been unsuccessful for RCC and therapy using immune modulators has had limited success, novel therapies enhancing further the immune system must be developed. MATERIALS AND METHODS: DCs were obtained from mouse bone marrow enriched for the haematopoietic progenitors, and cultured in the presence of interleukin-4 and granulocyte macrophage-colony stimulating factor. In vivo vaccines and in vitro proliferation assays were used to assess ability of the DCs to present tumour antigen. RESULTS: The presence of DCs was confirmed in the cultures by fluorescent-activated cell sorting analysis. In vivo, tumour-bearing animals receiving tumour extract-pulsed DCs as a vaccine showed a two to threefold reduction in tumour growth at day 12 and day 16 but no significant difference at day 28. In vitro, tumour extract-pulsed DCs stimulated significant proliferation of splenocytes from naive animals but not tumour-bearing animals. In addition, splenocytes from tumour-bearing animals had an attenuated immune response in vitro. CONCLUSION: These results show that it is possible to use the DC vaccine to modulate the immune response to achieve an antitumour effect, but further manipulation of the DC vaccine may be needed to overcome the tumour-induced immune suppression.