To achieve the objectives, various expertises are needed. Therefore, the partners from the Flemish biotech landscape (Ghent, Antwerp, Leuven and Brussels) put their weight behind the Persomed project.
How does the colorectal cancer vaccine work?
Reactivating the immune system
The purpose of immunotherapy is to reactivate the immune system so that the cancer cells are attacked and destroyed by the patient's immune system. The Persomed consortium has chosen to develop a cancer vaccine based on dendritic cells, the natural antigen-presenting cells of the immune system.
In addition to high medical effectiveness, the development of the personalized colorectal cancer vaccine focuses on the broad and affordable use of the new vaccine.
Dendritic cells with synthetic neoantigens
To develop a cancer vaccine, the researchers first identify cancer-specific peptides or neoantigens. These differ greatly from patient to patient.
In addition, monocytes are isolated from the blood of the patient, cultured for a short time in the laboratory and transformed into dendritic cells.
The cells are then pooled with synthetic neoantigens to produce a personalized vaccine.
Creating and multiplying cancer-killing cells
Via the vaccine, neoantigens are administered to the patient. The dendritic cells (green) absorb the neoantigens present in the vaccine (light green) and present them on their surfaces with the help of 'major histocompatibility complex' (MHC) proteins.
This elicits a response from the T cells (grey) which have a receptor for these neoantigens. The T cells will then differentiate into cell-killing effector 'killer' T cells which attack the cancer cells (black) in the patient's gut.
Step by step towards a personalized cancer vaccine
The cancer vaccine can only be administered when the patient already has cancer. The following steps are followed to arrive at the personalized vaccine for the patient in question:
The DNA sequences of cancer cells and normal cells of the patient are compared with a reference sample. The mutations are then further investigated to find out whether they result in amino acid changes in the encoded proteins.
Computer models are used to determine whether neoantigens can bind to major histocompatibility complex (MHC) molecules.
The sequence of the cancer RNA is determined to ensure that the DNA mutations are also present in the messenger RNA in the cancer cells.
Researchers will then check whether the neoantigens are present on the surface of the cancer cells and which neoantigens are best used in the cancer vaccine (validation).