In an attempt to capitalize on the strong inflammatory state induced by alloreactivity, Fotaki et al. infected monocyte-derived dendritic cells (DCs) with an infection-enhanced adenoviral vector (which could be used to encode a target antigen) and matured them with polyI:C, R848, and IFNγ. These DCs released pro-inflammatory cytokines and, when co-cultured with PBMCs, promoted the maturation of bystander DCs capable of cross-presenting a target antigen to CD8+ T cells, effectively activated T and NK cells, and promoted cytotoxic function.
Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-gamma (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state. COMBIG/Ad5M-matured allogeneic DCs (alloDCs) efficiently activated T-cells and NK-cells in allogeneic co-culture experiments. The secretion of immunostimulatory factors during the co-culture promoted the maturation of bystander-DCs, which efficiently cross-presented a model-antigen to activate antigen-specific CD8+ T-cells in vitro. We propose that alloDCs, in combination with Ad5M as loading vehicle, may be a cost-effective and logistically simplified DC vaccination strategy to induce anti-tumor immune responses in cancer patients.
Author Info: (1) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (2) Department of Immunology, Genetics, and Pathology, Scie
Author Info: (1) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (2) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (3) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (4) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (5) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Immunicum AB. (6) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. (7) Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
