Technical challenges in the manufacture of dendritic cell cancer therapies

Abstract

Dendritic cells (DCs) are the most potent antigen-presenting cells, owing to their ability to stimulate antigen-specific T cell responses. Their use as therapeutic cancer vaccines is, therefore, increasing rapidly. In order to manufacture DC vaccines, peripheral blood mononuclear cells (MNCs) are harvested by leukapheresis and enriched for monocytes by adherence to plastic, elutriation and/or CD14* selection. Differentiation of monocytes into immature DCs is then achieved by culture with cytokines. Critical issues for successful vaccination involve optimisation of cell collection, choice of antigen, antigen loading, route and schedule of administration. Regarding cell collection, apheresis systems are able to selectively collect MNCs, including monocytes, lymphocytes, CD34+ and DCs with low red blood cell, granulocyte and platelet content. This review describes the technical challenges of, and optimal procedures for, harvesting, enrichment, maturation, antigen loading and administration of DCs. Additionally, the requirement to further advance these procedures to develop this promising treatment, with the aim of achieving widespread clinical adoption of therapeutic DC-based cancer vaccines is discussed.