Promotors:
Karine Breckpot (Vrije Universiteit Brussel)
Project Partners:
Vrije Universiteit Brussel
Budget uitgereikt door Kom op tegen Kanker:
€69.732
Samenvatting
Cancer is currently the most frequent cause of death in Belgium, surpassing cardio-vascular diseases (gezondbelgie.be). Despite improvements in conventional therapies and the adoption of immunotherapy as a fourth pillar of cancer therapy, for a large number of patients still no durable cure is available, reflecting the need for additional treatment options. Oncolytic virus (OV) therapy is another promising strategy to further enhance our arsenal to fight cancer. OVs are viruses modified in such a way that they selectively infect, spread within and kill cancer cells, concomitantly providing immune stimulation, making them an excellent tool for cancer
treatment. Nevertheless, as is the case for other (immuno)therapies, response rates vary between patients. The success of cancer treatments, including OV therapy, depend on the way in which cancer cells die. So-called immunogenic cell death (ICD), which is accompanied by the release or exposure of several immune stimulatory components is instrumental for inducing potent antitumor responses. ICD in turn is strongly dependent on the type of cell death evoked by the treatment. Yet, for many treatments including OVs, the underlying cell death mechanisms (CDMs) are poorly understood. During the ongoing project, we successfully demonstrated that treatment of human melanoma cells with oncolytic herpes simplex virus type-1 (oHSV-1) results in the release of hallmark mediators of ICD. Moreover, we showed that oHSV-1 contributes to the maturation of patient-derived dendritic cells (DCs), both essential prerequisites for successful immune engagement. Following up on prior
findings by our group and others, we seek to shed more light on the actual CDM induced by oHSV-1 treatment. We hypothesize that gaining insight into the CDM will allow us to drive cell death into a more immunogenic direction, enhancing immunogenicity and ultimately enhancing anti-tumor immune responses.
treatment. Nevertheless, as is the case for other (immuno)therapies, response rates vary between patients. The success of cancer treatments, including OV therapy, depend on the way in which cancer cells die. So-called immunogenic cell death (ICD), which is accompanied by the release or exposure of several immune stimulatory components is instrumental for inducing potent antitumor responses. ICD in turn is strongly dependent on the type of cell death evoked by the treatment. Yet, for many treatments including OVs, the underlying cell death mechanisms (CDMs) are poorly understood. During the ongoing project, we successfully demonstrated that treatment of human melanoma cells with oncolytic herpes simplex virus type-1 (oHSV-1) results in the release of hallmark mediators of ICD. Moreover, we showed that oHSV-1 contributes to the maturation of patient-derived dendritic cells (DCs), both essential prerequisites for successful immune engagement. Following up on prior
findings by our group and others, we seek to shed more light on the actual CDM induced by oHSV-1 treatment. We hypothesize that gaining insight into the CDM will allow us to drive cell death into a more immunogenic direction, enhancing immunogenicity and ultimately enhancing anti-tumor immune responses.