About our research group/lab
Elucidating which antigens are presented both on professional antigen presenting dendritic cells (DCs) to initiate T cell responses, as well as on infected or malignant cells to be targeted by effector T cells, is key to design antigen-specific immunotherapy. Together with the EMC Proteomics Center (Dr. J Demmers) we analyse HLA-eluates to get insight into (the regulation of) antigen processing, presentation and recognition in DCs and target cells and to derive effective HLA-epitopes for immunotherapy. In the lab we use various immunological assays to further investigate the significance of identified epitopes and regulatory mechanisms for disease specific immune responses.
Chronic HBV and liver cancer
About 250 million people worldwide have a chronic HBV infection (cHBV) and at high risk to develop hepatocellular carcinoma (HCC). No effective treatment is available for either HCC or cHBV. A high potential form of clinically validated immunotherapy is Synthetic Long Peptide (SLP)-based vaccination. SLPs are linear amino acid sequences harboring multiple potential CD4+ and CD8+ T cell epitopes. Together with our clinical partners (Prof. R. de Man, Dr. D. Sprengers) and our private partner ISA Pharmaceuticals b.v. we are designing an SLP-based vaccine, based on the identified epitopes above, to treat cHBV and possibly in the future also HCC.
Yearly, 2400 new pancreatic ductal adeno carcinoma (PDAC) patients are diagnosed in the Netherlands and incidence is rising fast. Novel therapeutic options are urgently needed as 5-year survival is less than 10%. Peptides derived from mutated proteins and tumor associated antigens are presented on HLA and may render PDAC visible to T cells. These antigens could be exploited for antigen specific immunotherapy. Therefore, with the aim to design immunotherapy also for this deadly disease we use our expertise and infrastructure to study antigen presentation in PDAC.
Improving immunotherapy design
To optimize immunotherapy, we would like to know:
1) which disease-related peptides are most effectively presented in HLA I and II on diseased cells and DC, because only T cells recognizing these epitopes will be effective.
2) which HLA-peptides are immunogenic and (still) have the potential to induce T cells in patients.
3) which adjuvants or immune modulatory treatments can most effectively support antigen-based immunotherapy in each specific disease or even patient.
- Elevated serum levels of soluble CD14 in HBeAg-positive chronic HBV patients upon Peginterferon treatment are associated with treatment response. Dou Y, van Montfoort N, van den Bosch A, Janssen HLA, de Man RA, Buschow SI, Woltman AM. J Viral Hepat. 2019 May 15.
- TLR7 polymorphism, sex and chronic HBV infection influence plasmacytoid DC maturation by TLR7 ligands. Buschow SI, Biesta P, Groothuismink Z, Erler N, Vanwolleghem T, Ho E, Najera I, Ait-Goughoulte M, de Knegt R, Boonstra A, Woltman A, Antiviral Research 2018
- HBV-derived synthetic long peptide can boost CD4+ and CD8+ T cell responses in chronic HBV patients ex vivo. Dou Y, van Montfoort N, van den Bosch A, de Man RA, Zom GG, Krebber WJ, Melief CJM, Buschow SI, Woltman AM. J Infect Dis. 2017
- Transcriptional patterns associated with BDCA3 expression on BDCA1+ myeloid dendritic cells. van der Aa E, Biesta PJ, Woltman AM, Buschow SI. Immunol Cell Biol. 2017
- Hepatitis B Virus Surface Antigen Activates Myeloid Dendritic Cells via a Soluble CD14-Dependent Mechanism. van Montfoort N, van der Aa E, van den Bosch A, Brouwers H, Vanwolleghem T, Janssen HL, Javanbakht H, Buschow SI, Woltman AM. J Virol. 2016
- Hepatitis B virus infection affects BDCA3+ dendritic cell frequency and IFN- production. van der Aa E, Biesta PJ, Buschow SI, Janssen HLA, Woltman AM. PLOS One. 2016
- To target or not to target viral antigens in HBV related HCC? Buschow SI, Sprengers D, Woltman AM. J Hepatol. 2015
Collaboration within Erasmus MC
- Dr. J. Demmers, department of Biochemistry
- Dr. R. Debets, department of Medical Oncology
Collaboration outside of Erasmus MC
Diahann Jansen, PhD.; D.T.S.L.Jansen@erasmusmc.nl
M.T.A. de Beijer, Msc.; M.firstname.lastname@example.org
Rachid Bouzid, Msc.; R.Bouzid@erasmusmc.nl
Amy Kessler, Msc.; A.Kessler@erasmusmc.nl
Robbie Luiten, Bsc ; email@example.com
Linda Voogd Bsc.
Past members (from 2016)
Aniek van den Bosch
Past students (from 2016)
Muriel Aguilar Bretones
Janet de Wilde