About

Joke den Haan is professor in cellular immunology with a specific interest in the role of myeloid cells in adaptive immunity. She obtained her PhD from the University of Leiden in 1997 on the biochemical characterization of human minor histocompatibility antigens (cum laude) and did a post-doc at the University of Washington, Seattle, in the lab of Prof.dr. Mike J. Bevan on antigen cross-presentation by dendritic cell subsets (1998-2003). She joined the department of Molecular Cell Biology and Immunology in 2004 and her lab investigates the function of different types of macrophages and DCs subsets and develops cancer vaccines that specifically deliver antigens to these cell types to achieve optimal adaptive immune responses (please link to KWF movie). For these studies the group uses different types of in vitro, ex vivo, and in vivo model systems.

Research Line

Function of CD169-expressing macrophages and dendritic cells

CD169+ macrophages are localized at the marginal zone of the spleen and the subcapsular sinus of lymph nodes where they capture pathogens and extracellular vesicles. We have previously shown that antigens that are bound by splenic CD169+ macrophages are presented to B cells and transferred to cross-presenting dendritic cells that activate CD8+ and CD4+ T cell responses. We investigate the interactions of CD169+ macrophages with dendritic cells and other immune cells.

Figure 1. Mouse spleen with B cells in blue, red pulp macrophages in red and CD169+ macrophages in green.

Recently, a CD169-expressing Axl+ dendritic cell subset was discovered in human PBMC.  We can detect this cell type in healthy individuals and cancer patients and discovered that liposomal nanovaccines that bind to CD169 on these cells are taken up and presented to T cells.

Figure 2. Unsupervised tSNE analysis of dendritic cell subsets in human PBMC including CD169-expressing Axl+ DCs. (Affandi en al. submitted)

Development of cancer nanovaccines

We have generated different types of nanovaccines that target cancer antigens and adjuvant specifically to CD169+ macrophages and dendritic cells in mice and men. For this we utilize CD169-specific antibodies that are conjugated to cancer antigens in the form of proteins or peptides. In addition, we have generated liposomes that contain physiological ligands for CD169 to target cancer antigens and adjuvant to CD169+ macrophages and dendritic cells. Current studies are focused on the type of adjuvant and antigen to be included for optimal immune responses. In addition, we are generating nanobodies for human CD169 and will include them in different types of nanovaccins.

Figure 3. Outgrowth of melanoma tumor after vaccination with cancer antigen protein or peptide targeted to CD169+ macrophages (from van Dinther et al. 2018 Front in Immunol. 9: 1997)

Key publications

  1. Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma.
    Seretis A, Amon L, Tripp CH, Cappellano G, Hornsteiner F, Dieckmann S, Vierthaler J, Ortner-Tobider D, Kanduth M, Steindl R, Boon L, den Haan JMM, Lehmann CHK, Dudziak D, Stoitzner P.
    Vaccines (Basel). 2025 Mar 25;13(4):346. doi: 10.3390/vaccines13040346.
    PMID: 40333215 Free PMC article.
  2. Exploring CD169+ Macrophages as Key Targets for Vaccination and Therapeutic Interventions. Bouma RG, Wang AZ, den Haan JMM. Vaccines (Basel). 2025 Mar 20;13(3):330. doi: 10.3390/vaccines13030330. PMID: 40266235 Free PMC article. Review.
  3. Development of a Versatile Cancer Vaccine Format Targeting Antigen-Presenting Cells Using Proximity-Based Sortase A-Mediated Ligation of T-Cell Epitopes. Wang AZ, Brink HJ, Bouma RG, Affandi AJ, Nijen Twilhaar MK, Heijnen DAM, van Elk J, Maaskant JJ, Konijn VAL, Stolwijk JGC, Kalay H, Olesek K, van Kooyk Y, van der Schoot JMS, Bentlage AEH, Scheeren FA, Verdoes M, Vidarsson G, Kuijl CP, den Haan JMM. Bioconjug Chem. 2024 Nov 20;35(11):1805-1814. doi: 10.1021/acs.bioconjchem.4c00403. Epub 2024 Nov 7. PMID: 39511711
  4. Bouma, R.G., M.K. Nijen Twilhaar, H.J. Brink, A.J. Affandi, B.S. Mesquita, K. Olesek, J.M.A. van Dommelen, R. Heukers, A.M. de Haas, H. Kalay, M. Ambrosini, J.M. Metselaar, A. van Rooijen, G. Storm, S. Oliveira, Y. van Kooyk, and J.M.M. den Haan, Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity. Int J Pharm, 2024. 660: p. 124254

Group members

Alsya Affandi

Alsya Affandi, PhD

Postdoctoral researcher
My research focuses on developing nanovaccines targeting antigen-presenting-cells such as dendritic cells and macrophages, to stimulate T cell responses against cancer or pathogens. A variety of nanovaccine platforms are used including liposome and single-domain antibodies. For my research, I use spectral/imaging flow cytometry, immunoassays, microscopy, and analysis of single-cell RNA sequencing datasets.

Aru Wang

Aru Zeling Wang, MSc

PhD student
My project is to develop a versatile cancer vaccine format in which patient-specific tumor antigens can be conjugated to antibodies specific for dendritic cells to stimulate immune responses.

Rianne Bouma

Rianne Bouma, MSc

PhD student
My project focuses on creating a vaccine using novel molecules targeted to CD169+ macrophages. These molecules will be conjugated to liposomes which have cancer antigen encapsulated. This will elicit a macrophage/dendritic cell mediated immune response against the specific tumor.

Other PI's

Sue Gibbs

About Sue Gibbs is professor in Skin and Mucosa Regenerative Medicine. She is PI at the Department of Molecular Cell Biology & Immunology and also in the Department of Oral
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Febe van Maldegem

About Febe van Maldegem is associate professor and group leader in the Department of Molecular Cell Biology & Immunology. Her work focusses on the complex role of the tumour microenvironment
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Gijs Kooij

About Gijs Kooij is a PI (associate professor) at the Department of Molecular Cell Biology & Immunology as well as the MS center Amsterdam. His main research focus is to
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Elga de Vries

Research Line Neuro-immunology: The neurovascular unit in health and disease                   Altered activation of the immune system, neuroinflammation (marked by activated astrocytes and microglia), and dysfunction of
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Sandra van Vliet

About During her cum laude PhD and postdoctoral years Sandra J. van Vliet studied the impact of glycosylation and glycan-binding receptors on dendritic cell biology and specialized in the field
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Reina Mebius

About Reina Mebius is professor in Molecular Cell Biology at the Department of Molecular Cell Biology & Immunology. She has contributed to the field of lymphoid organ development showing that
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Yvette van Kooyk

About Yvette van Kooyk is professor in Molecular Cell Biology and Immunology,  head of the department Molecular Cell Biology and Immunology and PI of the Dendritic Cell Immunobiology group. Van Kooyk’s research
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Jack van Horssen

About Jack van Horssen is an Associate Professor at the Department of Molecular Cell Biology & Immunology. Driven by a passion for unraveling the causes of neurodegenerative diseases, his research
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Juan J. Garcia Vallejo

About Juan J. Garcia Vallejo is Associate Professor and Principal Investigator at the Department of Molecular Cell Biology & Immunology. Juan has always been interested in combining his medical background
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Marjolein van Egmond

About Marjolein van Egmond is professor in Oncology and Inflammation. She is PI at the Department of Molecular Cell Biology & Immunology and staff member at the Department of Surgery.
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