Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells

Abstract

Dendritic cells (DCs) are pivotal regulators of immune responses, specialized in antigen presentation and bridging the gap between the innate and adaptive immune system. Due to these key features, DCs have become a pillar of the continuously growing field of cellular therapies. Here we review recent advances in good manufacturing practice strategies and their individual specificities in relation to DC production for clinical applications. These take into account both small-scale experimental approaches as well as automated systems for patient care.

Cord-Blood-Derived Professional Antigen-Presenting Cells: Functions and Applications in Current and Prospective Cell Therapies

“…DC are key elements in modern cellular therapies with applications harnessing their multifaceted prowess as cellular vaccines in the treatment of, e.g., malignant cancers [ 188 ]. For instance, UCB-derived DC have been used in pilot phases of clinical trials of hematological disorders, including acute myeloid leukemia (AML) in pediatric patients [ 163 , 165 , 189 ].…”

Combined TLR-3/TLR-8 Signaling in the Presence of α-Type-1 Cytokines Represents a Novel and Potent Dendritic Cell Type-1, Anti-Cancer Maturation Protocol

“…Out of several different subsets that make up the DC compartment, namely conventional DCs (type-1 and type-2), plasmacytoid DCs, and monocyte-derived DCs (MoDCs), ex vivo generated MoDCs are still most widely utilized due to several operational advantages, such as the ability to obtain large numbers of cells that can be easily manipulated, e.g., cryopreserved for future use in case of repetitive administrations [ 3 ]. The manufacture of MoDC-based anti-tumor vaccines generally consists out of four basic steps: patient apheresis; monocyte selection; monocyte-to-DC differentiation using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4; and DC maturation along with TAA loading [ 4 ]. While the first three steps are more or less similar across various protocols, the maturation of DCs has varied greatly in the last few decades and most likely plays a major role in the clinical success of DC vaccines [ 5 ].…”

Antigen-Presenting Cells: Potential of Proven und New Players in Immune Therapies

“…DCs were also applied in combination with cytokine-induced killer cells to treat gastrointestinal tumors, lung cancer, and breast cancer, as well as hematological malignancies [15]. Their clinical effectiveness was markedly increased after methods for generation, cultivation, and manipulation to exploit the immune-activating potential of DCs had been improved [14, 16]. The protocols were substantially improved with respect to optimization and standardization to increase cell yield, reduction of culture time, the differentiation process, and antigen loading.…”

“…optimization of culture conditions for APCs and production under GMP (Good Manufacturing Practice) conditions [16, 22];…”

“…generation of new, highly specialized APCs after loading with tumor antigens or generation of leukemia-derived APCs from myeloid blasts ex vivo [16];…”