Tumour necrosis factor‐α (TNF‐α) transgene‐expressing dendritic cells (DCs) undergo augmented cellular maturation and induce more robust T‐cell activation and anti‐tumour immunity than DCs generated in recombinant TNF‐α

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Abstract
Tumour antigen presentation by dendritic cells (DCs) to T cells in lymphoid organs is crucial for induction of anti‐tumour immune responses. It has been previously reported that tumour necrosis factor‐α (TNF‐α) is required for DC activation and subsequent induction of optimal immune responses, and thus DCs for anti‐tumour vaccination are often generated by culture in exogenous TNF‐α. In the present study, we investigated the effect on anti‐tumour immunity of vaccination with Mut1 tumour peptide‐pulsed DCs engineered to express a TNF‐α transgene. Our data shows that transfection of DCs with recombinant adenovirus AdV‐TNF‐α resulted in greater maturation of the DCs than occurred with control DCs cultured in exogenous TNF‐α, as determined by up‐regulated expression of pro‐inflammatory cytokines (e.g. interleukins 1β and 18), chemokines [e.g. interferon‐γ‐inducible protein‐10 and macrophage inflammatory protein‐1β (MIP‐1β)], the CC chemokine receptor CCR7, and immunologically important cell surface molecules (CD40, CD86 and intercellular adhesion molecule‐1). These transgenic DCs stimulated stronger allogeneic T‐cell responses in vitro and T‐cell activation in vivo; displayed 2·4‐fold enhanced chemotactic responses to the MIP‐3βin vitro (PPMut1 peptide‐pulsed, AdV‐TNF‐α‐transfected DCs stimulated more efficient in vitro Mut1‐specific CD8+ cytotoxic T‐cell responses and solid tumour immunity in vivo, when compared to the in vitro TNF‐α‐cultivated DCs. Thus, DCs engineered to secrete TNF‐α may offer a new strategy in DC cancer vaccines.