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Mimicking pathogens; an integrated nano-medicine approach to developing intelligent cancer vaccines

Final Report Summary - PATHFINDER (Mimicking pathogens; an integrated nano-medicine approach to developing intelligent cancer vaccines.)

The medical revolution during the last century has improved quality of life and expanded life expectancy by almost 20 years. Two major steps that contributed to this progress have been the development of effective vaccines as prophylaxis against infectious diseases and the development of antibiotics to eliminate infections that could otherwise not be controlled. Nevertheless, many patients still enter hospitals as a result of improper immune function, caused by the lack of a sufficiently strong immune response not only against infectious diseases but also to combat cancer.
During the past decades, we have translated basic discoveries on the immune system’s functioning into clinical practice. We developed cancer vaccines based on one of the most potent immune cells, the dendritic cell (DC). Based on the core competences, In the PATHFINDER project we embraced chemical biology as a new discipline to design groundbreaking novel cancer vaccines. Two major approaches have been followed:

I In vivo imaging and targeting of the immune system
To evaluate if vaccines are effective in patients, it is most important to trace the fate of dendritic cell vaccines in vivo after injection and monitor the outcome of immune intervention in real-time in patients by imaging techniques such as MRI, PET/CT and scintigraphy. We developed, a clinically applicable biodegradable PLGA nanoparticle platform was developed, to further develop in vivo monitoring, especially tracking of therapeutic cells in patients.
Similarly, we fabricated nanoparticles for therapeutic vaccination purposes. Nanoparticles containing tumor antigen and adjuvants to activate dendritic cells, and coated with antibodies to target dendritic cells in vivo were proven effective in preclinical animal models. A next step is to develop these particles for clinical applications. This would be a major improvement, as instead of isolating dendritic cells from each individual patient, highly standardized and mass-produced nanoparticles can be used as fully synthetic cancer vaccines to target dendritic cells in vivo.

II Chemical immunology and synthetic dendritic cells
An alternative approach is to reproduce the function of immune cells by synthesizing artificial dendritic cells. To develop such new chemistry-driven immune-therapeutics, the PATHFINDER program integrated two research fields – medical immunology and chemical biology – that have only interacted fragmentarily thus far. In this fundamentally different approach we aim to construct fully synthetic parts of the immune system exploiting supramolecular chemistry and bio-orthogonal chemistry.
In a simplified model, each cell can be considered as an input signaling – output module, where the environment is sampled, interpreted and results in a certain cellular response. As a first approximation, we successfully build a supramolecular output module containing immune signals, capable of stimulating killer T cells directed against tumour cells.
Although still in its infancy, initial results from this part of the PATHFINDER ERC program are extremely exciting.
It is clear that in this era of personalized medicine there are major challenges but also opportunities for immunologists and chemists to develop entirely novel diagnostic and therapeutic tools. As becoming clear from this ERC pathfinder program, completely new directions are taken to obtain a catalogue of novel tools to not only develop radically differently designed synthetic vaccines, but also tools to measure the direct consequences of these immune interventions in real-time in patients.