Nanobody-targeted photodynamic therapy to kill cancer

Informazioni relative al progetto

KILLCANCER

ID dell’accordo di sovvenzione: 677582

DOI

10.3030/677582

Progetto chiuso

Data della firma CE 27 Aprile 2016

Data di avvio 1 Luglio 2016

Data di completamento 31 Dicembre 2021

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 500 000,00

Contributo UE

€ 1 500 000,00

Coordinato da

UNIVERSITEIT UTRECHT
Netherlands

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

Periodo di rendicontazione: 2021-01-01 al 2021-12-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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