Clinical cancer vaccines against nonviral antigens

Introduction Preventive vaccination against infectious diseases is considered one of the most successful health measures of all time. Therapeutic vaccination against established diseases such as persistent infections and cancer has proven much more challenging, because the vaccine intervention must combat an immune system that has been restrained by tolerizing or polarizing mechanisms that sustain the disease in a misguided attempt at self-tolerance. Nevertheless, recent clinical results indicate that the era of successful therapeutic vaccination has arrived. In this Review, we discuss the most attractive preclinical and clinical therapeutic vaccination strategies, as well as opportunities to improve such therapies. With the exception of some forms of premalignant disease, the proportion of patients benefiting from treatment with cancer vaccines, in addition to the mean survival advantages, leaves much to be desired. Better results can most likely be obtained by a better choice of antigens, improvements in vaccine design, and appropriate cotreatments. The latter can alleviate immunosuppressive mechanisms in the cancer microenvironment and boost vaccine performance by appropriate stimulation or modulation of the immune system.