The importance of material selection in the differentiation of monocytes into dendritic cells

By: Natasha Boghosian, Robert Pleydon and David Smith
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INTRODUCTION

Cell therapy is an emerging market with the potential to shift the paradigm for how diseases are treated. In recent years, the ‘cancer immunotherapy’ subset of the market has seen rapid growth garnered from the efficacy of the often personalized treatment approach. Named ‘Breakthrough of the Year’ by Science magazine in 2013, the immunotherapy market has started to really come to fruition in the past few years, including the recent FDA approval of Novartis’ CAR-T therapy, Kymriah™ (tisagenlecleucel) and Kite’s CAR-T therapy, Yescarta™ (axicabtagene ciloleucel) [1–3].

One of the earlier areas of research and development in immunotherapy was in the use of dendritic cell (DC)-based treatments. DCs, often considered the most potent of the antigen presenting cells (APC), play a key role in connecting the innate and adaptive immune system [4,5]. Akin to a billboard, DCs process and then present antigens on their surfaces in order to appropriately activate T cells for immune attacks. This presentation and activation step is often the missing link in an immune response to cancer as the signal is not appropriately processed by the DC when the cancer is seen as ‘self’. To tackle this, many researchers have looked to exploit the function of DCs through the culturing of monocytes, differentiation to DCs, and modifying DCs with appropriate tumor signals ex-vivo. This causes immune system stimulation upon re-infusion of activated, mature DCs (Figure 1) [6].

Although there are several early and late stage clinical trials leveraging this approach, there is currently only one, commercially available dendritic-based therapy in the USA [6]. Provenge^® (Sipuleucel-T) was commercialized by Dendreon in 2010 and is still available for the treatment of advanced prostate cancer [7]. Recent market reports have anticipated an annual growth rate for the ‘Global Dendritic Cell & Tumor Cell Cancer Vaccine’ of 20.7% until 2030 [8].

With increasing interest in bringing cell-based products to fruition comes the increasing importance of selecting appropriate systems and materials for manufacturing. This paper will focus on reviewing material properties and important factors to consider when choosing a container for culture. With that, it also critical to consider process steps upstream (e.g., enrichment) and downstream (e.g., harvest) of culture as well as ancillary materials (e.g., medium and cytokines) when deciding on and developing a complete manufacturing process [10–12].