Nanobody-targeted photodynamic therapy to kill cancer

Projektinformationen

KILLCANCER

ID Finanzhilfevereinbarung: 677582

DOI

10.3030/677582

Projekt abgeschlossen

EK-Unterschriftsdatum 27 April 2016

Startdatum 1 Juli 2016

Enddatum 31 Dezember 2021

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 500 000,00

EU-Beitrag

€ 1 500 000,00

Koordiniert durch

UNIVERSITEIT UTRECHT
Netherlands

Periodic Reporting for period 4 - KILLCANCER (Nanobody-targeted photodynamic therapy to kill cancer)

Berichtszeitraum: 2021-01-01 bis 2021-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Current cancer therapies often fail to cure patients. Ideally, a cancer therapy should locally eradicate the cancer and should be capable of creating a memory to protect from recurrences.
Photodynamic therapy (PDT) is a treatment approach in which cancer cells are killed with compounds, named photosensitizers that are activated locally through light exposure. Importantly, PDT eradication of cancers commonly involves the immune system. However, current PDT is only partly cancer specific and patients remain sensitive to light for several weeks.
Recently, I have developed an improved version of targeted PDT that uses very small antibodies, i.e. nanobodies, to target the photosensitizer. Nanobodies distribute homogenously, bind rapidly and specifically to cancer cells, resolving the issues of PDT.
Within the KILLCANCER project we have been focusing on better understanding the mechanism of nanobody-targeted PDT, its potential to induce tumor regression in vivo, and its capacity to trigger the immune system. In addition, we have been preparing for stepping into the veterinary clinic and test our treatment in spontaneously developing cancers in companion animals, namely cats with oral cancer.
The outcome of this research has scientifically advanced the new field of nanobody-targeted PDT, by providing essential information on its mechanism of action. Current efforts are in evaluating this treatment in the veterinary clinic, which will give insights into the feasibility of this approach in human cancer patients, to ultimately improve current cancer treatment.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

We have been able to:
- test the principle of nanobody-targeted photodynamic therapy with different molecular targets in vitro (i.e. tumor markers)
- observe the effects of nanobody-targeted PDT on cancer cells and normal tissue, in living animals
- demonstrate that some damage associated molecular patterns such as HSP70 are exposed or released after this treatment, that dendritic cells become activated once in contcat with tumor cells treated this way and and T cells proliferate
- determine that EGFR is a relevant tumor marker in oral cancer in cats
- demonstrate that nanobody-targeted PDT is a safe and very effective treatment, after one single treatment session.

A summary of the outcome of this research cam be found here: https://doi.org/10.54050/PRJ1218398

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

We have:
- developed nanobodies for endothelial cell targeting
- identified the immune effects triggered by nanobody-targeted PDT
- evaluated nanobody-targeted PDT in feline cell lines
- obtained very encouraging results with one single treatment in mice with human tumors.

Nanobody-targeted PDT compared to conventional PDT