Personalized dendritic cell-based tumor immunotherapy

Abstract

Advances in the understanding of the immunoregulatory functions of dendritic cells (DCs) in animal models and humans have led to their exploitation as anticancer vaccines. Although DC-based immunotherapy has proven clinically safe and efficient to induce tumor-specific immune responses, only a limited number of objective clinical responses have been reported in cancer patients. These relatively disappointing results have prompted the evaluation of multiple approaches to improve the efficacy of DC vaccines. The topic of this review focuses on personalized DC-based anticancer vaccines, which in theory have the potential to present to the host immune system the entire repertoire of antigens harbored by autologous tumor cells. We also discuss the implementation of these vaccines in cancer therapeutic strategies, their limitations and the future challenges for effective immunotherapy against cancer.

Keywords: anticancer immune response; chaperone protein; dendritic cell; idiotype; personalized tumor vaccine; tumor lysate.

Figure 1. Ex vivo preparation of dendritic cell-based anticancer vaccines

Vaccine generation includes: choosing the source of DC, their ex vivo expansion, loading with tumor antigen, maturation/activation and in vivo delivery. The primary source of DC currently used in clinical trials and in most animal studies consists of myeloid DCs derived from the blood (for clinical trials) or bone marrow precursors (for most animal studies). Further activation with cytokines/chemokines, TLR-ligands or growth factors leads to maturation of the differentiated DCs. Different approaches have been evaluated to load DCs with tumor-specific antigens that include tumor-derived peptide/protein, RNA/DNA, total lysates, apoptotic or necrotic tumor cells, chaperone proteins, exosomes or tumor cell–DC fusion. DCs may be administered intravenously, intradermally, subcutaneously or by intranodal or intratumoral injection. DC: Dendritic cell; TLR: Toll-like receptor.

Figure 2. Tumor-induced immunosuppresion affects DC-based vaccine efficiency

The tumor microenvironment (including immunosuppressive factors produced by tumor cells such as TGF-β, IL-10, VEGF and IDO) may promote the generation and expansion of immunosuppressive cells (e.g., Tregs, iDC, pDC and MDSCs). These immunoregulatory cells or these immunosuppressive factors impair the therapeutic efficiency of DC-based vaccines and foster tumor progression. DC: Dendritic cell; iDC: Immature DC; IDO: Indoleamine 2,3-dioxygenase; mDC: Mature DC; MDSC: Myeloid-derived suppressor cell; pDC: Plasmacytoid DC; Treg: Regulatory T cell.