Breakthrough Concepts in Immune-oncology: Cancer Vaccines at the Bedside

Clinical approval of the immune checkpoint blockade (ICB) agents for multiple cancer types has reinvigorated the long-standing work on cancer vaccines. In the pre-ICB era, clinical efforts focused on the Ag, the adjuvants, the formulation, and the mode of delivery. These translational efforts on therapeutic vaccines range from cell-based (e.g., dendritic cells vaccine Sipuleucel-T) to DNA/RNA-based platforms with various formulations (liposome), vectors (Listeria monocytogenes), or modes of delivery (intratumoral, gene gun, etc.). Despite promising preclinical results, cancer vaccine trials without ICB have historically shown little clinical activity. With the anticipation and expansion of combinatorial immunotherapeutic trials with ICB, the cancer vaccine field has entered the personalized medicine arena with recent advances in immunogenic neoantigen-based vaccines. In this article, we review the literature to organize the different cancer vaccines in the clinical space, and we will discuss their advantages, limits, and recent progress to overcome their challenges. Furthermore, we will also discuss recent preclinical advances and clinical strategies to combine vaccines with checkpoint blockade to improve therapeutic outcome and present a translational perspective on future directions.