Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

Abstract

Dendritic cells (DCs) have shown great potential as a component or target in the landscape of cancer immunotherapy. Different in vivo and ex vivo strategies of DC vaccine generation with different outcomes have been proposed. Numerous clinical trials have demonstrated their efficacy and safety in cancer patients. However, there is no consensus regarding which DC-based vaccine generation method is preferable. A problem of result comparison between trials in which different DC-loading or -targeting approaches have been applied remains. The employment of different DC generation and maturation methods, antigens and administration routes from trial to trial also limits the objective comparison of DC vaccines. In the present review, we discuss different methods of DC vaccine generation. We conclude that standardized trial designs, treatment settings and outcome assessment criteria will help to determine which DC vaccine generation approach should be applied in certain cancer cases. This will result in a reduction in alternatives in the selection of preferable DC-based vaccine tactics in patient. Moreover, it has become clear that the application of a DC vaccine alone is not sufficient and combination immunotherapy with recent advances, such as immune checkpoint inhibitors, should be employed to achieve a better clinical response and outcome.

Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy

“…Adoptive transfer approaches, based on the administration of ex-vivo mRNA-transfected DCs, were the first form of mRNAbased vaccines to be proposed and clinically investigated (Baldin et al, 2020). Most of these clinical studies employed DCs generated from peripheral blood monocytes (Baldin et al, 2020).…”

“…Adoptive transfer approaches, based on the administration of ex-vivo mRNA-transfected DCs, were the first form of mRNAbased vaccines to be proposed and clinically investigated (Baldin et al, 2020). Most of these clinical studies employed DCs generated from peripheral blood monocytes (Baldin et al, 2020). However, thanks to the recent advancements in separation techniques for primary DCs, the new generation of DC vaccines is focusing on the isolation of specific primary DC subsets, due to their superior immunostimulatory functions (Baldin et al, 2020).…”

“…Most of these clinical studies employed DCs generated from peripheral blood monocytes (Baldin et al, 2020). However, thanks to the recent advancements in separation techniques for primary DCs, the new generation of DC vaccines is focusing on the isolation of specific primary DC subsets, due to their superior immunostimulatory functions (Baldin et al, 2020). Despite DC vaccines have shown encouraging outcomes in preclinical studies, their clinical efficacy remains limited.…”

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

“…The most recent clinical trials surrounding DC vaccines focus on improving the ex vivo steps required to make the vaccine in order to increase efficiency [128]. These improvements aim to diminish the effects of the TME (Figure 5).…”

“…Therefore, recent research into DC vaccines has been aimed at improving DC activation and promoting of T cell function, as well as the use of adjuvant treatments alongside DC vaccines to counteract the effect of an immunosuppressive TME [127]. The most recent clinical trials surrounding DC vaccines focus on improving the ex vivo steps required to make the vaccine in order to increase efficiency [128]. These improvements aim to diminish the effects of the TME (Figure 5).…”