Project Details
Description
With an overall 5-year survival of only 20% for advanced-stage ovarian cancer (OC) patients, long-term effective therapies against OC are an unmet clinical need. Targeted therapies were able to improve progression-free survival,
though patients still relapse. Moreover, immunotherapy has so far not resulted in clear patient benefit. Importantly, the role of dendritic cells (DCs) as a key player in mounting an adaptive immune response has not been investigated yet in OC. Interestingly, our lab has uncovered that vaccination with tumor-derived DCs can elicit a therapeutically
relevant immune response resulting in decreased tumor growth.
Therefore, in this project, we will evaluate the DC heterogeneity in OC and the potential to use tumor-derived DCs
as a vaccine to treat OC. For this, we designed 4 aims. First, we aim to generate a mouse model for OC that is
similar to patients in terms of tumor progression so that mouse-to-human translatability can be ensured. Second, we
aim to achieve an in-depth characterization of the general immune compartment in OC tumor-bearing versus control mice while particularly focusing on DCs. Third, we aim to compare the immune compartments of mouse and patient OC samples. Fourth, we will determine the effectiveness of using the different DC populations as anti-cancer
vaccines in the newly generated mouse model for OC. The results of this project will provide new insights into the role of DCs in OC using a highly patient translatable mouse model and will propose a novel therapeutic approach for OC that could overcome the currently witnessed barriers to effective therapeutic responses.
While Aims 1 to 3 are either already achieved or are currently ongoing, receiving this honorable fellowship will mainly fund the 4th aim of the project, which focuses on developing the DC vaccine against OC.
though patients still relapse. Moreover, immunotherapy has so far not resulted in clear patient benefit. Importantly, the role of dendritic cells (DCs) as a key player in mounting an adaptive immune response has not been investigated yet in OC. Interestingly, our lab has uncovered that vaccination with tumor-derived DCs can elicit a therapeutically
relevant immune response resulting in decreased tumor growth.
Therefore, in this project, we will evaluate the DC heterogeneity in OC and the potential to use tumor-derived DCs
as a vaccine to treat OC. For this, we designed 4 aims. First, we aim to generate a mouse model for OC that is
similar to patients in terms of tumor progression so that mouse-to-human translatability can be ensured. Second, we
aim to achieve an in-depth characterization of the general immune compartment in OC tumor-bearing versus control mice while particularly focusing on DCs. Third, we aim to compare the immune compartments of mouse and patient OC samples. Fourth, we will determine the effectiveness of using the different DC populations as anti-cancer
vaccines in the newly generated mouse model for OC. The results of this project will provide new insights into the role of DCs in OC using a highly patient translatable mouse model and will propose a novel therapeutic approach for OC that could overcome the currently witnessed barriers to effective therapeutic responses.
While Aims 1 to 3 are either already achieved or are currently ongoing, receiving this honorable fellowship will mainly fund the 4th aim of the project, which focuses on developing the DC vaccine against OC.
| Acronym | ANI392 |
|---|---|
| Status | Active |
| Effective start/end date | 1/11/24 → 31/10/25 |