TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines.

Cancer vaccines have offered unrequited hope as a mechanism for rapidly and potently eliciting a patient's immune system to counter tumors. Initial results from preclinical mouse models have not translated to substantial benefit to patients, suggesting that either the targets or the vaccination approach were inadequate. Recent innovations in antigen identification have spiked renewed interest vaccination technologies. This has coincided with a detailed molecular understanding of the coordinated steps in postactivation support of T cell proliferation, differentiation and survival, leading to the development of novel targets and combinations that are substantially more effective than first and second generation cancer vaccines in preclinical models. Within this cluster of developments, the TNF-receptor superfamily members have emerged as attractive candidates for clinical implementation. Here we review recent developments in the mechanisms of action of TNFRSF agonists, and how their activity is potentiated by integration co-targeting pattern recognition receptors.