Generation of immunogenic and tolerogenic clinical-grade dendritic cells

Abstract

Immunotherapy with dendritic cells (DCs) that have been manipulated ex vivo to become immunogenic or tolerogenic, has been tested in clinical trials for disease therapy. DCs are sentinels of the immune system, which after exposure to antigenic or inflammatory signals and crosstalk with effector CD4+ T cells express high levels of costimulatory molecules and cytokines. Suppression of either costimulatory molecules or cytokines generates tolerogenic DCs (TDCs), which induce T regulatory cells (Tregs) and a state of tolerance. Nevertheless, DC vaccination is still at an early stage, and improvements are mainly needed in generating clinical-grade DC products and in quality control of monitoring assays to assess the effect of DC vaccination in future clinical trials. Here, we review the recent work in DC generation and monitoring approaches for DC-based trials with immunogenic or tolerogenic DCs.

Effect of Dexamethasone on Phenotyping of Dendritic Cells: In vitro and in vivo Study

“…Isolation and culture of human heparinized peripheral blood buffy coats provide a valuable model for studies on DCs biology and may help uncover new means to manipulate DCs differentiation and function in therapeutic settings (Kalantari et al, 2011). In the present study, the buffy coat layer from human peripheral blood was cultured in the presence of GM-CSF and IL-4 to generate dendritic cell populations which were allowed to differentiate into mature DCs within 9 days.…”

EFFICIENCY EVALUATION OF THE HOME-PRODUCED RECOMBINANT HUMAN CYTOKINES FROM the sci-store.ru FOR GENERATION OF MONOCYTE-DERIVED DENDRITIC CELLS

“…Однако выделение этих клеток из крови или тканей является трудоемким и дорогостоящим процессом и часто не позволя-ет получить значительного количества клеток, необходимого для экспериментов, особенно если объектом исследования являются ДК человека. Поэтому ДК, полученные из моноцитов in vitro, остаются самым распространенным объектом исследований иммуностимулирующих или толе-рогенных функций ДК [3,5], процессов их созре-вания и апоптоза [1], а также внутриклеточного сигналинга в ДК [7]. Моноцитарные ДК также используются в работах по фармакологии, на-правленных на поиск иммунотропных препара-тов и совершенствование вакцин [6].…”

“…До сих пор наиболее надежным методом полу-чения моноцитарных ДК [5] [12]. На первом этапе этого метода из моноцитов получают не-зрелые ДК с помощью культивирования с ин-терлейкином-4 (IL-4) и гранулоцитарно-макро-фагальным колониестимулирующим фактором (GM-CSF).…”

Tolerogenic dendritic cells and their applications in transplantation

“…11,12 Recent studies have focused on the prospective value of tol-DCs to induce clinical organ graft tolerance and to prolong graft survival. [13][14][15] Here, we provide an overview of the characteristics of tol-DCs, describe their biological functions and highlight recent advances that may yield DC-based therapeutic opportunities.…”