Virus-like liposomes targeting CD169+ dendritic cells as a novel carrier for cancer immunotherapy

Assoc. Prof. Dr. J. den Haan1), University of Amsterdam/The Netherlands

Prof. Dr. Y. van Kooyk1), University of Amsterdam/The Netherlands

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Assoc. Prof. Dr. Joke den Haan and Prof. Dr. Yvette van KooykDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC – location VUmc, The Netherlands


Cancer is accounting for 26% of all deaths worldwide. While the introduction of checkpoint inhibitors has dramatically changed the outlook of some cancers, only a fraction of all cancer patients benefits from these therapies, mainly due to a failed immune cell activation directed to the tumor.1) Classical vaccination approaches have so far failed to boost sufficiently strong immune responses to combat cancer, and therefore there is an urgent need for new strategies to be developed to induce effective anti-tumor immune responses.2)

In this study, we propose the development of virus-like liposomes as a novel dendritic cell-targeted vaccination strategy in which we will use ligands of CD169 molecules expressed on antigen presenting cells, immune-activating viral-mimic molecules as adjuvant, and encapsulated tumor antigens.3)4) Using combination of in vitro assays and in vivo models, this study will investigate the efficacy of virus-like liposomes as novel nano-vaccine carriers that targets CD169+ antigen presenting cells for cross-presentation and tumor-specific T cell activation.

Benefit for the community

The prognosis of cancer patients, especially those diagnosed late in disease progression, is extremely poor. Therefore, new types and better therapies are urgently needed. Our aim is to develop a vaccination strategy that can be combined with other immunotherapies to prolong survival and to contribute to a better quality of life for cancer patients.

Visit the supervisors lab

Dr Joke den Haan and Prof Yvette van Kooyk

Trujillo JA, Sweis RF, Bao R, Luke JJ, 2018
T Cell-Inflamed versus Non-T Cell-Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection
Cancer Immunol. Res. 6, 990-1000
Bol KF, Schreibelt G, Gerritsen WR, de Vries IJ, Figdor CG, 2016
Dendritic Cell-Based Immunotherapy: State of the Art and Beyond
Clin. Cancer Res. 22, 1897-906
Crocker PR, Kelm S, Dubois C, Martin B, McWilliam AS, Shotton DM, Paulson JC, Gordon S, 1991
Purification and properties of sialoadhesin, a sialic acid-binding receptor of murine tissue macrophages
EMBO J. 10, 1661-1669
van Dinther D, Veninga H, Iborra S, Borg EGF, Hoogterp L, Olesek K, Beijer MR, Schetters STT, Kalay H, Garcia-Vallejo JJ, Franken KL, Cham LB, Lang KS, van Kooyk Y, Sancho D, Crocker PR, den Haan JMM, 2018
Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming
Cell Rep. 22, 1484-1495
Publications derived from the project:
Affandi AJ, Olesek K, Grabowska J, Nijen Twilhaar MK, Rodríguez E, Saris A, Zwart ES, Nossent EJ, Kalay H, de Kok M, Kazemier G, Stöckl J, van den Eertwegh AJM, de Gruijl TD, Garcia-Vallejo JJ, Storm G, van Kooyk Y, den Haan JMM, 2021
CD169 Defines Activated CD14(+) Monocytes With Enhanced CD8(+) T Cell Activation Capacity
Front. Immunol. 12, 697840
Grabowska J, Affandi AJ, van Dinther D, Nijen Twilhaar MK, Olesek K, Hoogterp L, Ambrosini M, Heijnen DAM, Klaase L, Hidalgo A, Asano K, Crocker PR, Storm G, van Kooyk Y, den Haan JMM, 2021
Liposome induction of CD8(+) T cell responses depends on CD169(+) macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion
J. Controlled Release 331, 309-320
Grabowska J, Stolk DA, Nijen Twilhaar MK, Ambrosini M, Storm G, van der Vliet HJ, de Gruijl TD, van Kooyk Y, den Haan JMM, 2021
Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8(+) T Cell Responses via CD169(+) Macrophages and cDC1
Vaccines (Basel) 9, 56
Nijen Twilhaar MK, Czentner L, van Nostrum CF, Storm G, den Haan JMM, 2021
Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines
Pharmaceutics 13, 954
Nijen Twilhaar MK, Czentner L, Bouma RG, Olesek K, Grabowska J, Wang AZ, Affandi AJ, Belt SC, Kalay H, van Nostrum CF, van Kooyk Y, Storm G, den Haan JMM, 2022
Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses
Front. Immunol. 13, 842241
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