Dendritic cells for active immunotherapy: Optimizing design and manufacture in order to develop commercially and clinically viable products

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions

“…Conventional maturation protocols use a combination of the cytokines IL-1β, IL-6, TNF-α and prostaglandin E2, which are capable of inducing the differentiation of mature DCs with great co-stimulatory capacity and migration ability, but with reduced capacity of production of IL-12 (32,33).…”

Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy

“…As discussed above, most clinical trials performed hitherto have relied on monocytes as precursor cells for DC vaccine manufacturing (Supplemental Video) (Gilboa, 2007;Tacken et al, 2007;Chiang et al, 2015). Monocytes can be isolated from leukapheresis harvests by various techniques, including centrifugal elutriation, adherence, or immunomagnetic selection using anti-CD14 mAb-coated magnetic beads (Table 2) (Nicolette et al, 2007). Given the fact that moDCs are by far the most frequently used DC type in clinical trials, we will only address here the current strategies for optimizing moDC culture protocols (Fig.…”

“…Tumor antigens can be derived from either "undefined" or "defined" antigen sources (Nicolette et al, 2007). Undefined antigen preparations contain both known and unknown epitopes (Nicolette et al, 2007); examples used in the setting of DC therapy for AML are peptides eluted from the tumor cell surface, whole AML cell preparations for fusion with DCs, necrotic AML cell lysates (e.g., prepared by repeated freeze-thaw cycles), apoptotic AML cells (e.g., prepared by g-irradiation), total tumor RNA extracted from the AML cells, and AML cell-derived extracellular vesicles (van der Pol et al, 2012) including exosomes (small vesicles of endosomal origin released from live cells) and apoptotic blebs (large vesicles released from cells undergoing apoptosis) Anguille et al, 2012c;Yao et al, 2014). Sources of defined antigens are synthetic peptides or nucleic acids encoding a specific tumor antigen Anguille et al, 2012c).…”

“…The main advantage of using undefined antigen preparations is that they cover the full repertoire of antigens expressed by the tumor cells (Schui et al, 2002;Nicolette et al, 2007;Tesfatsion, 2014). At the same time, this is also considered to be their major disadvantage.…”

Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection

“…With the successful production of viral supernatants in three of four HIV-1 ϩ subjects, the procedure was scaled up for clinical use. Large-scale, clinical-grade DC preparation is routine and has been broadly used with peripheral blood products obtained from patients with cancer or HIV-1 infection in our and other laboratories (5,17,18,21,26,30). Although the entire HIV-1 vaccine production process is complex, it was shown to be feasible and applicable to the controlled good manufacturing practice setting.…”