Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response.
Fusion of dendritic cells and tumor cells (FCs) constitutes a promising tool for generating an antitumor response because of their capacity to present tumor antigens and provide appropriate costimulatory signals. CD40-CD40L interaction has an important role in the maturation and survival of dendritic cells and provides critical help for T-cell priming. In this study, we sought to improve the effectiveness of FC vaccines in a murine model of B-cell lymphoma by engineering FCs to express CD40L by means of an adenovirus encoding CD40L (Adv-CD40L). Before transduction with Adv-CD40L, no CD40L expression was detected in FCs, DCs or tumor cells. The surface expression of CD40L in FC transduced with Adv-CD40L (FC-CD40L) ranged between 50 and 60%. FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction. Furthermore, FC-CD40L showed enhanced migration to secondary lymphoid organs. Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-gamma, compared with controls. Treatment with the FC-CD40L vaccine induced regression of established tumors and increased survival. Our data demonstrate that FC transduced with Adv-CD40L enhances the antitumor effect of FC vaccines in a murine lymphoma model and this is associated with an increased Th17-type immune response.
Alvarez
E
E
Department of Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Moga
E
E
Barquinero
J
J
Sierra
J
J
Briones
J
J
D000256:Adenoviridae; D000818:Animals; D023201:CD40 Ligand / Q000276:immunology*; D002459:Cell Fusion / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic / Q000379:methods*
D023201:CD40 Ligand