Human PBMC-derived dendritic cells transduced with an adenovirus vector induce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro

Abstract

Dendritic cells (DC) are among the most potent antigentor encoding bacterial ␤-galactosidase (␤-gal) under the presenting cells known and play an important role in the transcriptional control of a CMV promoter was used to initiation of antigen-specific T-lymphocyte responses. Sevtransduce DC at multiplicities of infection (MOI) up to 1000. eral recent studies have demonstrated that DC expressing While high MOI were required to achieve efficient transducvector-encoded tumour-associated antigens can induce tion there was no significant effect on DC morphology, protective and therapeutic immunity in murine cancer modimmunophenotype or potency in allogeneic lymphocyte els. In the current study we set out to examine in vitro the proliferation assays. Furthermore, transduced DC-induced utility of adenovirus vectors in the transduction of human antigen-specific CTL activity against adenoviral proteins DC for the induction of antigen-specific T-lymphocyte and more significantly, the vector-encoded antigen ␤-gal. responses against a defined vector-encoded antigen. DC These data clearly demonstrate the potential of adenovirus were derived from the adherent fraction of PBMC by culvectors in anticancer DC vaccine strategies and provide ture in defined medium containing GM-CSF and IL-4. A an important link between existing animal data and human replication-defective E1/E3-deleted type 5 adenovirus vecclinical application.

Priming of T cells with aAd-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8+ T cells: implications for an efficient vaccination strategy

“…As previously shown, the adenoviral transduction did not have any influence on the maturation state of the resulting DC population. 19,[22][23][24] In mice, the use of DC infected with tumor-associated Ag for immunization and the induction of T-cellmediated protective immunity resulting in the reduction of established tumors could be demonstrated. Immunization with Ad-DC induced long-lasting antitumor activity even after single administration when compared to the direct injection of Ad-gp100 alone.…”

“…In addition, most investigators used immature, peptide-pulsed or infected DC for priming and restimulation of CD8 + T cells. 22,23,[26][27][28][29] Philip et al showed that immature DC loaded with MART-1 peptide or infected with an adenoviral construct were functionally equivalent in the induction of peptide-specific CTL in vitro. 27 We have recently shown that peptide-pulsed immature DC are inferior to mature DC in inducing peptide-specific T-cell responses in vitro.…”

Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity

“…In preliminary experiments, we have observed that Adtransduced DC can effectively activate melanoma-specific CD8 + CTL in vitro, thus confirming recently published reports. 14,19 It remains to be determined how the immunosuppressive effects described in this report will impact on the induction of antigen-specific cellular immune responses with Ad-transduced DC.…”

Tumors Suppress In Situ Proliferation of Cytotoxic T Cells by Promoting Differentiation of Gr-1+ Conventional Dendritic Cells through IL-6

“…Adenoviral vectors encoding OVA or GFP were prepared, purified, and titrated as described previously (19). Ag-specific T cell responses…”