Effective treatment of established
tumors requires rational multicombination
immunotherapy strategies designed to target all functions of the patient immune system and
tumor immune microenvironment. While these combinations build on the foundation of successful
immune checkpoint blockade antibodies, it is increasingly apparent that successful
immunotherapy will also require a
cancer vaccine backbone to engage the immune system, thereby ensuring that additional immuno-oncology agents will engage a
tumor-specific immune response. This review summarizes ongoing clinical trials built upon the backbone of
cancer vaccines and focusing on those clinical trials that utilize multicombination (3+) immuno-oncology agents. We examine combining
cancer vaccines with multiple checkpoint blockade
antibodies, novel multifunctional molecules, adoptive
cell therapy and immune system agonists. These combinations and those yet to enter the clinic represent the future of
cancer immunotherapy. With a
cancer vaccine backbone, we are confident that current and coming generations of rationally designed multicombination
immunotherapy can result in effective
therapy of established
tumors.