Ramping up antigen presentation

To be effective in cancer immunotherapy, tumor antigens must be efficiently processed and presented to T cells by antigen-presenting cells (APCs), of which dendritic cells are considered to be the most potent. On page 1273 Irvine et al. present a way to efficiently transfect dendritic cells ex vivo using a cationic peptide to condense and mediate cell uptake of a DNA construct encoding the antigen. They go on to show that dendritic cells transfected in this manner effectively stimulate T cells to develop antigen-specific cytotoxic T-lymphocyte (CTL) activity. Mice injected with the transfected dendritic cells developed antigen-specific immune responses and fended off tumors more robustly than mice injected with dendritic cells pulsed with the antigen peptide.

In a related study, Laus et al. focused on improving uptake of extracellular antigens into APCs for vaccine development. Such soluble antigens are notoriously poor at stimulating CTL responses because they have difficulty gaining entry to APCs that process and present them to the CTLs. Laus et al. have overcome this barrier by adding charge-modifying peptide sequences to the antigen to counteract the repulsive cell surface charge and promote endocytosis of the antigen. They also coupled the antigen to a fusogenic peptide that disrupts the endosomal membrane to release the antigen into the cytosol, making it more accessible to the MHC class I antigen presentation machinery, and boosting the levels of specific CTL immunity in vivo (see p. 1269).