The favored method for delivering cancer immunotherapy has been dendritic cells: they are the central antigen-presenting cells for generating T cell responses; they can be grown in vitro in large quantities; and their use in mice with cancer led to some spectacular results. “That led to a whole wave of excitement,” says Pardoll. “But it hasn't really panned out.”
Perhaps the biggest problem is tolerance. Most cancer immunotherapy focuses not on tumor-specific antigens, which vary too much because each tumor has different mutations, but on self-antigens that are overexpressed in the tumor. Although some collateral damage of normal self-tissue is alright for many tissues, the real problem is getting the immune response off the ground when it is challenged with a self-antigen.
Now Yang et al. show that viral but not dendritic cell vectors can do the job. Only the viral vectors can suppress tolerance to a cancer self-antigen in a mouse model, thus leading to increased survival. Ligands that activate TLRs also do the trick, and may be more promising in humans, as humans generally mount antibody responses that neutralize viral vectors. ▪