Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model

Abstract

Recent investigations have demonstrated that adenoviral and lentiviral vectors encoding HER-2 can be utilized in cancer immunotherapy. However, it is not known whether both viral systems elicit a similar immune response. Here, we compare the immune response in mice induced by dendritic cells (DCs) infected with either recombinant adenovirus or lentivirus encoding rat HER-2 (rHER-2). Both vaccine types yielded similar control of tumor growth, but we found clear differences in their immune responses 10 days after DC immunization. Adenovirus rHER-2-transduced DCs elicited locally and systemically high frequencies of CD4+ and CD8+ T cells, while lentivirus rHER-2-transduced DCs predominantly led to CD4+ T-cell infiltration at the tumor site. Splenocytes from mice immunized with lentivirus rHER-2-transduced DCs secreted higher levels of interferon (IFN)-γ, mainly by CD4+ T cells, following stimulation by RM-1-mHER-2 tumors. In contrast, the adenovirus vaccinated group exhibited CD4+ and CD8+ T cells that both contributed to IFN-γ production. Besides an established cellular immune response, the rHER-2/DC vaccine elicited a significant humoral response that was highest in the adenovirus group. DC subsets and regulatory T cells in the spleen were also differentially modulated in the two vaccine systems. Finally, adoptive transfer of splenocytes from both groups of immunized mice strongly inhibited in vivo tumor growth. Our results suggest that not only the target antigen but also the virus system may determine the nature and magnitude of antitumor immunity by DC vaccination.

A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

“…Immunotherapy is regarded as a potential approach to eliminate MTB [22,23]. The vehicles used to deliver specific antigens are very important in immunotherapy [24,25]. Lentiviral vectors serve as good candidates because they have been proved to be highly efficient for in vivo gene delivery and stable long-term expression of transgene in several target tissues.…”

Harnessing autophagy for cell fate control gene therapy

“…41 The DNA was mixed into a PEI solution and then added dropwise to the cells. After 48 and 72 h of incubation at 37°C, the viral supernatants were collected and concentrated by ultracentrifugation.…”

Engineering lentiviral vectors for modulation of dendritic cell apoptotic pathways

“…In the context of DC vaccines, LVs permit high TAA gene transfer efficiencies and expression [17], the generation of a broad repertoire of presented peptides, the induction of more stable peptide-MHC complexes, and the ability to co-express multiple genes such as TAAs and survival factors [18]. Along these lines we previously demonstrated that LVs encoding the sequence for the xeno-TAA (rat) HER-2 efficiently transduced murine bone marrow-derived DCs [19]. Furthermore, when these transduced DCs were injected into mice harboring murine HER-2-positive tumors, potent systemic CD4 and CD8 T cell responses along with humoral responses were generated that significantly inhibited tumor growth [19].…”

“…Along these lines we previously demonstrated that LVs encoding the sequence for the xeno-TAA (rat) HER-2 efficiently transduced murine bone marrow-derived DCs [19]. Furthermore, when these transduced DCs were injected into mice harboring murine HER-2-positive tumors, potent systemic CD4 and CD8 T cell responses along with humoral responses were generated that significantly inhibited tumor growth [19]. …”