Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses.

Autor:	Nijen Twilhaar MK; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Czentner L; Department of Pharmaceutics, Faculty of Science, Utrecht University, Utrecht, Netherlands., Bouma RG; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Olesek K; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Grabowska J; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Wang AZ; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Affandi AJ; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Belt SC; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Kalay H; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., van Nostrum CF; Department of Pharmaceutics, Faculty of Science, Utrecht University, Utrecht, Netherlands., van Kooyk Y; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Storm G; Department of Pharmaceutics, Faculty of Science, Utrecht University, Utrecht, Netherlands.; Department of Biomaterials Science and Technology, Faculty of Science and Technology, University of Twente, Enschede, Netherlands.; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., den Haan JMM; Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 18; Vol. 13, pp. 842241. Date of Electronic Publication: 2022 Feb 18 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.842241
Abstrakt:	Cancer vaccination aims to activate immunity towards cancer cells and can be achieved by delivery of cancer antigens together with immune stimulatory adjuvants to antigen presenting cells (APC). APC maturation and antigen processing is a subsequent prerequisite for T cell priming and anti-tumor immunity. In order to specifically target APC, nanoparticles, such as liposomes, can be used for the delivery of antigen and adjuvant. We have previously shown that liposomal inclusion of the ganglioside GM3, an endogenous ligand for CD169, led to robust uptake by CD169-expressing APC and resulted in strong immune responses when supplemented with a soluble adjuvant. To minimize the adverse effects related to a soluble adjuvant, immune stimulatory molecules can be incorporated in liposomes to achieve targeted delivery of both antigen and adjuvant. In this study, we incorporated TLR4 (MPLA) or TLR7/8 (3M-052) ligands in combination with inflammasome stimuli, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) or muramyl dipeptide (MDP), into GM3 liposomes. Incorporation of TLR and inflammasome ligands did not interfere with the uptake of GM3 liposomes by CD169-expressing cells. GM3 liposomes containing a TLR ligand efficiently matured human and mouse dendritic cells in vitro and in vivo , while inclusion of PGPC or MDP had minor effects on maturation. Immunization with MPLA-containing GM3 liposomes containing an immunogenic synthetic long peptide stimulated CD4 + and CD8 + T cell responses, but additional incorporation of either PGPC or MDP did not translate into stronger immune responses. In conclusion, our study indicates that TLRL-containing GM3 liposomes are effective vectors to induce DC maturation and T cell priming and thus provide guidance for further selection of liposomal components to optimally stimulate anti-cancer immune responses. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Nijen Twilhaar, Czentner, Bouma, Olesek, Grabowska, Wang, Affandi, Belt, Kalay, van Nostrum, van Kooyk, Storm and den Haan.)
Databáze:	MEDLINE
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