Rabbit anti-Human CD70 polyclonal antibody

The use of tumor-associated antigen (TAA) mRNA for therapeutic purposes is under active investigation. To be effective, mRNA vaccines need to deliver activation stimuli in addition to TAAs to dendritic cells (DC). In this study, we evaluated whether intranodal delivery of TAA mRNA together with TriMix, a mix of mRNA encoding CD40 ligand, constitutive active Toll-like receptor 4 and CD70, results in the in situ modification and maturation of DCs, hence, priming of TAA-specific T cells. We showed selective uptake and translation of mRNA in vivo by lymph node resident CD11c(+) cells. This process was hampered by codelivery of classical maturation stimuli but not by TriMix mRNA. Importantly, TriMix mRNA induced a T-cell-attracting and stimulatory environment, including recruitment of antigen-specific CD4(+) and CD8(+) T cells and CTLs against various TAAs. In several mouse tumor models, mRNA vaccination was as efficient in CTL induction and therapy response as vaccination with mRNA-electroporated DCs. Together, our findings suggest that intranodal administration of TAA mRNA together with mRNA encoding immunomodulating molecules is a promising vaccination strategy. Cancer Res; 72(7); 1661-71. (C) 2012 AACR.

Epstein Barr virus (EBV) is a potent B cell transforming pathogen in humans. In most persistently EBV-infected individuals, potent cytotoxic lymphocyte responses prevent EBV-associated pathologies. In addition to comprehensive adaptive T cell responses, several innate lymphocyte populations seem to target different stages of EBV infection and are compromised in primary immunodeficiencies that render individuals susceptible to symptomatic EBV infection. In this mini-review, I will highlight the functions of natural killer, gamma delta T cells, and natural killer T cells during innate immune responses to EBV. These innate lymphocyte populations seem to restrict both lytic replication and transforming latent EBV antigen expression. The mechanisms underlying the recognition of these different EBV infection programs by the respective innate lymphocytes are just starting to become unraveled, but will provide immunotherapeutic strategies to target pathologies that are associated with the different EBV infection programs.