Advances in Human Dendritic Cell-Based Immunotherapy Against Gastrointestinal Cancer

Abstract

Dendritic cells (DCs), the strongest antigen-presenting cells, are a focus for orchestrating the immune system in the fight against cancer. Basic scientific investigations elucidating the cellular biology of the DCs have resulted in new strategies in this fight, including cancer vaccinology, combination therapy, and adoptive cellular therapy. Although immunotherapy is currently becoming an unprecedented bench-to-bedside success, the overall response rate to the current immunotherapy in patients with gastrointestinal (GI) cancers is pretty low. Here, we have carried out a literature search of the studies of DCs in the treatment of GI cancer patients. We provide the advances in DC-based immunotherapy and highlight the clinical trials that indicate the therapeutic efficacies and toxicities related with each vaccine. Moreover, we also offer the yet-to-be-addressed questions about DC-based immunotherapy. This study focuses predominantly on the data derived from human studies to help understand the involvement of DCs in patients with GI cancers.

Keywords: dendritic cells; gastrointestinal cancers; immunotherapy; patients; vaccines.

Figure 1

Schematic overview of DC-based CRC vaccines. DC-based vaccines consist of two main approaches: in vitro generated DC vaccines and in vivo DC-targeting vaccines. In vivo DC targeting is a vaccine approach to deliver antigens directly to DCs in vivo using chimeric targets composed of an anti-DC receptor antibody and an antigen. In vitro-generated vaccines often used monocyte-derived DCs. Briefly, DCs are generated by culture of monocytes in the presence of GM-CSF and IL-4 (or IFN-α), which are then loaded with tumor-associated antigens (TAAs). After maturation, TAA-loaded DCs are injected into CRC patients.