Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

Abstract

Over the years research in the field of cancer immunotherapy has flourished, bringing about crucial breakthroughs, but at the same time revealing new and important pathways of immune suppression that put a break on the success of cancer immunotherapy. This review focuses on how nano-and micromaterials can be used to induce antitumor immune responses and what their role in overcoming immune suppression could be. It is now beyond question that this requires elegantly designed particles that can reach their target cells, deliver antigenic cargo and most importantly immune stimulants in order to provoke and sustain antitumor immunity.3

Evading innate immunity in nonviral mRNA delivery: don’t shoot the messenger

“…Although knowledge of the cellular pathways involved in vector-mediated mRNA transfection expands by the day, their interaction with cellular components and the subsequent effects on cell function have been strongly overlooked so far. Evidence is emerging which indicates that most carriers exhibit an intrinsic immune-stimulating activity, inducing cell signaling cascades even without mRNA complexation [72].…”

Le vaccin ARN, une approche prometteuse pour la réactivation du système immunitaire dans la lutte contre le cancer

“…Ainsi, on observe, d'une part, un défaut d'activation des LT par les cellules dendritiques (DC) dans les ganglions, cellules dendritiques qui sont elles-mêmes inhibées par le contexte tumoral [1] ; d'autre part, une « paralysie » des LT activés ayant infiltré les tumeurs (ou tumor-infiltrating lymphocyte -TIL), ce qui les empêche d'éliminer les cellules tumorales [1] ( Figure 1). Les points de contrôles immunitaires sont des récepteurs de régulation négative présents à la surface des LT, tels que CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) et PD-1 (programmed death 1), dont l'engagement par leurs ligands exprimés par les cellules tumorales ou des cellules immunosuppressives du microenvironnement 1 bloque la fonction des LT [2].…”

“…Cependant, dans un grand nombre de cancers, le système immunitaire est dérégulé par la tumeur afin qu'il ne puisse plus protéger l'organisme du développement tumoral (Figure 1). [2], ou sur la suppression des LT régulateurs immunosuppresseurs [1]. La seconde approche repose sur des stratégies visant à stimuler les propriétés des cellules dendritiques.…”

Multifunctional nanoparticles for cancer immunotherapy

“…The production of such cellular immune responses firstly requires loading of the DCs with TAAs, after which the cells need to be matured, in order to become potent APCs. 18 Generally, in contrast to viruses and pathogenic bacteria, tumor cells don't have any danger signal to stimulate DCs maturation. Thus, an in vivo applicable nanoparticulate system for cancer vaccination should not only deliver antigen, but also exhibit immune adjuvant effects and induce complete maturation of the antigen-loaded DCs.…”

“…9 Therefore, cancer vaccine should be able to overcome this tumor-mediated immune suppression and to shift the balance back from immune suppression toward immune stimulation. 18 Nanoparticle-based immunotherapy which is the focus of current review paper is a new promising approach that can satisfy these requirements for developing the next generation of cancer Figure 1. The Cancer-Immunity Cycle The generation of immunity to cancer is a cyclic process that can be self propagating, leading to an accumulation of immune-stimulatory factors that in principle should amplify and broaden T cell responses.…”