Cancer-specific CD4 and CD8 T cell immunity

T lymphocytes are key in immune control of cancer, since they can specifically recognize and kill cancer cells. Most current immunotherapies stimulate tumor-specific T lymphocytes in a non-specific way e.g. by immune checkpoint antibodies, now commonly used in the clinic. We aim to develop more specific immunotherapies by identifying (neo)antigens in individual tumors which are used to design patient-specific immunotherapies. Using exome sequencing information and MHC peptide elution followed by mass spectrometry we can identify specific peptide sequences recognized by tumor-specific T cells.

We currently study the specificity and functionality of CD8 and CD4 T cells in the immune control of cancer using flow cytometry and high end single cell assays and in vivo imaging studies to improve their effector capacities.

Antigen presentation and dendritic cell biology

For optimal T cell activation it is key to understand the processing and MHC presentation of antigenic peptides as well as the biology of dendritic cells in lymphoid and non-lymphoid tissues. We study antigen handling of dendritic cell subsets in relation to antigen processing pathways, subcellular trafficking and proteasome and peptidase activities. The effects of dendritic cell activation by innate signals like TLR signaling and interaction with CD4 T helper cells are subject of study. We aim to understand these processes to optimally activate T cell functions to eradicate cancer cells or modulate the tumor microenvironment  for adequate immunotherapy.

Molecularly defined cancer vaccines

We use model antigens, oncogenic viruses and neoantigens to design molecularly defined cancer vaccines. Vaccine delivery systems such as Toll like receptor ligand based dendritic cell targeting, nanoparticles formulations and defined DNA vaccines are analysed as cancer therapeutics in preclinical murine models. Currently, synthetic peptide-based T cell vaccines conjugated to chemically well-defined TLR ligands are prepared in-house at GMP level and explored for immunotherapy of cancer patients.

Our research aims are to combine of therapeutic cancer vaccination with checkpoint inhibition, amelioration of the tumor immune environment with classical and novel ablative treatments like photodynamic therapies which are anticipated to result in major improvements of clinical benefit.

Our key collaborators within LUMC are the groups of R Arens, J. Borst, J.W Drijfhout (Immunology), T. van Hall, S. van der Burg, F. Speetjens, H. Gelderblom (Medical Oncology), N. de Miranda (Pathology), P. van Veelen (CPM). Within the University Leiden: D. Filippov, S. van Kasteren, J. Codee, G. van der Marel (Organic Chemistry) and W. Jiskoot, J. Bouwstra (LACDR).

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