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  • Cell-Based Therapy
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Cell-Based Therapy

Transfected human dendritic cells to induce antitumor immunity

Abstract

Dendritic cells are professional antigen-presenting cells able to prime naive T lymphocytes and regulate steadily the delicate balance between tolerance and activation during the immune response. In past years several reports have shown that genetically engineered dendritic cells (DCs) can be a powerful tool for inducing an antigen-specific immune response. The use of such modified antigen-presenting cells is a real working hypothesis in preclinical studies and in clinical vaccination approaches for cancer treatment. The definition of optimal transfection conditions for preserving DC survival and functionality is necessary to design a correct immunotherapeutic protocol. Different lipid-based transfection compounds were studied for their effects on DC survival, phenotype and functional properties. All the transfection procedures were able to select DCs with a higher expression of activation and costimulatory molecules (ie MHCII-DR, CD83, CD86, CD25) than the untreated DCs. However, only two compounds (LipofectAMINE PLUS and FuGENE 6), preserved or even increased the immunopotency of DCs as antigen-presenting cells. These protocols were applied to modify DCs in order to express an epithelial tumor-associated antigen, MUC1, and such cells were able to induce in vitro a specific immune response in healthy donors.

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Acknowledgements

We thank Dr A Lanzavecchia for the kind gift of the IL4.6 cell line and Dr J Taylor-Papadimitriou for providing the MoAbs HMFG1, HMFG2 and SM3. The MoAbs BC2 and Ma552 were generous gifts of Dr IFC McKenzie and Dr O Nilsson (CanDiagnostic), respectively. We thank Menarini Ricerche for providing us with the expression vectors pMRS 30 and pMRS 169. This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), European Communities Fifth Program QLRT-1999-00217 and Ministero per l'Universita e Ricerca Scientifica (MURST 40% and 60%).

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Rughetti, A., Biffoni, M., Sabbatucci, M. et al. Transfected human dendritic cells to induce antitumor immunity. Gene Ther 7, 1458–1466 (2000). https://doi.org/10.1038/sj.gt.3301266

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