Dendritic Cell-Based Cancer Vaccines

Abstract

Dendritic cells (DC) are specialized immune cells that play a critical role in promoting an immune response against Ags, which can include foreign pathogenic Ags and self-tumor Ags. DC are capable of boosting a memory T cell response but most importantly they are effective initiators of naive T cell responses. Many years of studies have focused on the use of DC vaccines against cancer to initiate and shape an antitumor-specific immune response and/or boost existing spontaneous antitumor T cell responses. In this study we give a brief overview of DC biology, function, and cellular subsets, and review the current status of the field of DC as cancer vaccines.

Figure 1

DC are effective initiators of immune responses against self and non-self-antigens. In addition to phagocytosis and macropinocytosis, DC are equipped with a variety of receptors for antigen uptake. Pathogens, tumor cells and dying cells can be detected by DC through different molecules that serve as environmental sensors. After antigen uptake and processing, peptide antigens are presented to T cells via MHC I and MHC II complexes, while lipid antigens are presented through CD1 family molecules. The expression of chemokine receptors allows DC to migrate to secondary lymphoid organs containing T cells. In addition to antigen presentation, DC also provide costimulatory signals for effective T cell activation. Furthermore, DC can also produce cytokines that not only influence the type of T cell response generated, but also allow for cross-talk with other immune cells such as NK cells, macrophages and B cells.

Figure 2

The state of the art in translating DC vaccines to the clinic. A schematic is shown which describes the key steps in preparation of DC vaccines for cancer therapy, including large scale blood draw, generally via a leukapheresis procedure, followed by elutriation into monocyte and lymphocyte fractions, or other magnetic bead-based purification of subsets. The desired progenitor cells are cultured with growth factors and differentiation factors to obtain the immature cells ready for antigen loading. The antigen can take many forms, including peptides, proteins, nucleic acids and cells. The antigen loaded DC are often matured with other cytokines, growth factors or toll-like receptor ligands, and then prepared for injection, which can be via many different routes.