Dendritic Cell-Based Vaccines

Abstract

Dendritic cells (DCs) acquire, process, and present antigens to T-cells, and provide the stimulatory signals and cytokines required to induce T-cells to proliferate and differentiate into effector cells. For this reason, infusion of in vitro-generated antigen-loaded DCs cells has been investigated as a vaccination strategy to elicit T-cell-mediated responses, particularly in the context of cancer where DC function in vivo is often blunted or subverted by factors released by the tumor. While studies in mice have repeatedly shown that DC-based vaccines can delay or prevent tumor progression, human clinical trials have been disappointing in comparison, offering only marginal benefit for patients. There is therefore still a need to improve the stimulatory capacity of the injected cells by improving antigen-loading strategies, refining differentiation and maturation protocols, and considering how to encourage stimulatory interactions with innate cells that may help sustain cytokine production in vivo. Perhaps the most significant hurdles to effective immunotherapy are the inhibitory “checkpoints” that are commonly hijacked by tumors to suppress T-cell function. We argue that a promising avenue for DC-based vaccination may be in combinatorial approaches, where the vaccines are used to elicit T-cell responses with desired properties for immune protection, while immune checkpoint blockade is used to sustain those immune responses in the face of tumor-induced suppressive activities.