NOD/scid IL-2Rg(null) mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo.

Journal of Translational Medicine
Stefani SprangerDolores J Schendel

Abstract

To date very few systems have been described for preclinical investigations of human cellular therapeutics in vivo. However, the ability to carry out comparisons of new cellular vaccines in vivo would be of substantial interest for design of clinical studies. Here we describe a humanized mouse model to assess the efficacy of various human dendritic cell (DC) preparations. Two reconstitution regimes of NOD/scid IL2Rg(null) (NSG) mice with adult human peripheral blood mononuclear cells (PBMC) were evaluated for engraftment using 4-week and 9-week schedules. This led to selection of a simple and rapid protocol for engraftment and vaccine evaluation that encompassed 4 weeks. NSG recipients of human PBMC were engrafted over 14 days and then vaccinated twice with autologous DC via intravenous injection. Three DC vaccine formulations were compared that varied generation time in vitro (3 days versus 7 days) and signals for maturation (with or without Toll-like receptor (TLR)3 and TLR7/8 agonists) using MART-1 as a surrogate antigen, by electroporating mature DC with in vitro transcribed RNA encoding full length protein. After two weekly vaccinations, the splenocyte populations containing human lymphocytes were recovered 7 days later an...Continue Reading

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Methods Mentioned

BETA
ELISA
FACS
flow cytometry
xenograft

Software Mentioned

SLT
FlowJo

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