Optimizing Dendritic Cell-Based Immunotherapy: Tackling the Complexity of Different Arms of the Immune System

Abstract

<jats:p>Earlier investigations have revealed a surprising complexity and variety in the range of interaction between cells of the innate and adaptive immune system. Our understanding of the specialized roles of dendritic cell (DC) subsets in innate and adaptive immune responses has been significantly advanced over the years. Because of their immunoregulatory capacities and because very small numbers of activated DC are highly efficient at generating immune responses against antigens, DCs have been vigorously used in clinical trials in order to elicit or amplify immune responses against cancer and chronic infectious diseases. A better insight in DC immunobiology and function has stimulated many new ideas regarding the potential ways forward to improve DC therapy in a more fundamental way. Here, we discuss the continuous search for optimal in vitro conditions in order to generate clinical-grade DC with a potent immunogenic potential. For this, we explore the molecular and cellular mechanisms underlying adequate immune responses and focus on most favourable DC culture regimens and activation stimuli in humans. We envisage that by combining each of the features outlined in the current paper into a unified strategy, DC-based vaccines may advance to a higher level of effectiveness.</jats:p>

Tracking and evaluation of dendritic cell migration by cellular magnetic resonance imaging

“…14,16 The issues of DC vaccine design and preparation are beyond the scope of this review and have been addressed recently by others. 16,18 However, critical to the success of the ex vivo-prepared DC-based vaccine approach is that the injected Ag-loaded DC must locate to a lymph node either via migration from a remote injection site or via direct intranodal injection. Early research recognized this concept to be a limitation as only 3-5% of the injected DCs actually migrate to a target lymph node.…”

Laser vaccine adjuvants

“…Use of LVA for therapeutic vaccines The versatility of dendritic cells (DC) and their key role in regulating adaptive immunity 167,168 has led to extensive investigation of DC-based vaccines for cancer and chronic infectious diseases. 168,169 Activation of cognate T cells in the dLN is also necessary.…”

“…168,169 Activation of cognate T cells in the dLN is also necessary. 170 For such vaccines, the intradermal delivery route offers a way to generate superior T-cell induction.…”

Dendritic cell immunotherapy in uterine cancer

“…The quality of the induced CD8 + T cells is influenced by the expression of co-stimulatory molecules, such as CD80, CD86, CD137, and CD252 on DC, the cytokine secretion pattern of DC and the type of CD4 + helper T cell response. [17][18][19] DC maturation is one of the crucial factors. 20,21 Currently, the "golden standard" used to mature DC consists of a cocktail of pro-inflammatory cytokines (IL-1β, IL-6, TNFα) and prostaglandin E 2.…”