Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response
Por:
Alvarez, E, Moga, E, Barquinero, J, Sierra, J, Briones, J
Publicada:
1 abr 2010
Resumen:
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. Gene Therapy (2010) 17, 469-477; doi: 10.1038/gt.2009.150; published online 10 December 2009
Filiaciones:
Alvarez, E:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08041, Spain
Moga, E:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08041, Spain
Barquinero, J:
Hosp Univ Vall Hebron, Ctr Tejidos & Terapia Celular Banco Sangre & Teji, Barcelona, Spain
Sierra, J:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08041, Spain
Briones, J:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08041, Spain
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