Abstract
Dendritic cell (DC)-based tumor vaccination holds great potential and is intensively being studied in cancer immunotherapy. Although DC vaccination can result in a survival advantage as shown in various cancer types, there is still room for improvement. Therefore, current DC vaccines urge rigorous optimization in order to increase their immune stimulating capacities for induction of antitumor immunity. In this context, strategies where the interleukin (IL) 15 transpresentation mechanism is incorporated, appear to be of great value due to the activating potential of IL-15 towards IL-15Rβγ expressing cells, such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. In the past 5 years, our research group designed different strategies to generate IL-15-expressing DC with superior T cell and NK cell-activating properties. In this review, we briefly describe the design of our latest DC vaccine, in which DC are genetically engineered to transpresent IL-15 via mRNA electroporation and discuss the capacity of this newly designed DC vaccine to activate NK cells and CTLs. Overall, IL-15 transpresenting DC show the potential to activate antitumor immunity and are promising candidates for DC based cancer immunotherapy.
Highlights
Already more than four decades ago, dendritic cells (DC) were described as the main orchestrators of the immune system [1]
We describe the effects of the IL-15 transpresentation mechanism on DC-mediated activation of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs)
DC vaccination can result in a survival advantage of cancer patients, there is a general agreement among cancer researchers that the true clinical benefit of DC based cancer immunotherapy has not been attained yet [10]
Summary
Already more than four decades ago, dendritic cells (DC) were described as the main orchestrators of the immune system [1]. Due to their capacity to induce antigen-specific CTL responses, DC-based vaccines were introduced in clinical trials to treat cancer patients, exactly two decades ago [2,3]. We describe the effects of the IL-15 transpresentation mechanism on DC-mediated activation of NK cells and CTLs. the potential of this optimized DC vaccine in combinatorial antitumor immunotherapy approaches is discussed.
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