Dr. Koen van der Maaden

Research

Cancer immunotherapy, defined as the ability to mobilise the host’s own immune system to kill cancer, has taken a central role in oncology. Unprecedented clinical responses in patients coinciding with the development of novel classes of immunotherapeutic drugs has been reported. One of the major challenges is to understand how to administer these molecules avoiding the risk of causing serious systemic toxicity and/or autoimmunity. Complementary, recent studies have shown that specific immunotherapy by means of peptide vaccination can result in the induction of tumour-killing T cells in patients. However, current formulations result in side effects and suboptimal priming and activation of T cells. Therefore, with my team we are focussing on designing and developing technologies for precision delivery of vaccines and immunomodulators, and therapeutic T cell vaccine formulation strategies.

1. Development of therapeutic T cell vaccines:

In this facet of my research line, the objective is to initiate the induction of new cancer-specific T cells through vaccination. Central to this endeavour is the utilization of dendritic cells (DCs), which play a pivotal role in the induction of cancer-specific T cells. To optimize this process, we are focussing on two aspects:

i) Targeting the skin — an organ naturally rich in DCs. To achieve this, we are developing devices for intradermal delivery, with a particular emphasis on microneedles. Microneedles are effective intradermal vaccine delivery devices that enter the skin without reaching blood vessels and pain receptors, and can result significant improved immune responses with lower antigen doses.

ii) Designing nanoparticle-based vaccine formulations, especially liposomes, that exhibit effective uptake of peptide-based antigens by dendritic cells, thereby enhancing the proliferation and potentiation of cancer-specific T cells. To enable translation of the liposome technology we focus on developing GMP-compliant formulation methods.

2. Reactivation of suppressed T cells within the tumour:

Another dimension of my research line involves reactivating T cells that are suppressed within the tumour microenvironment. This comprises:

i) Development of injection devices for precision delivery of immunotherapeutic agents into the tumour microenvironment. This ensures targeted delivery, aiming to minimize the risk of adverse effects on healthy tissues and maximizing the impact on the tumour.

ii) Designing drug formulations that cause retained high therapeutic drug doses inside the tumour microenvironment, thereby reducing administration frequencies and reducing expensive drug usage.

Curriculum Vitae

I studied Pharmacy (BSc) at Utrecht University (2004-2008), followed by a Master's in Bio-Pharmaceutical Sciences at Leiden University in (2008-2010) for which I graduated with honours. Sequentially, I secured a Ph.D. position at the Division of Drug Delivery Technology, focusing on "Microneedle-mediated vaccine delivery". For my PhD I graduated with honours and received the C.J. Kok prize (best PhD thesis of the year of the faculty of Science of Leiden university). In 2014 I developed vaccine formulations for nanoporous microneedles at IntraVacc (Bilthoven). Additionally, I designed a digitally-controlled microneedle applicator, now commercialized by start-up uPRAX Microsolutions. From 2015-2019, I did a postdoc research at Leiden University focussing on liposomal cancer vaccines and microneedle-based intradermal vaccination. Subsequently, I held a postdoctoral position in a SME in Germany (2019-2021) focusing on intratumoral injection devices, funded by a personal EU H2020 grant. In 2022, I fulfilled a postdoc position at Leiden University, overseeing PhD students in the development of intradermal vaccine delivery devices. Since 2023, I am establishing my research line within the Department of Immunology, emphasizing on liposomal cancer vaccine formulations and devices for precision delivery.