Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Pierre Coulie, Institut de Duve, Belgium
- Second opponent: Professor Oddbjørn Straume, Haukeland University Hospital
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, University of Oslo
Chair of the Defence
Professor Ludvig Munthe, University of Oslo
Principal Supervisor
Professor Eivind Hovig, University of Oslo
Summary
This project aimed to elucidate the immunological mechanisms induced by the investigational treatment UV1 in combination with checkpoint inhibition. UV1, a cancer vaccine candidate developed by the Norwegian company Ultimovacs, was the subject of our investigation. The research included a comprehensive analysis of the induced T cell response through cell culturing and phenotyping. By administering UV1, we stimulate an immune response against telomerase, hypothesizing that a CD4+ T cell response against a critical tumor-associated antigen will lead to enhanced cancer cell killing and improved clinical outcomes for treated patients.
We compared the dynamics of the immune response across three of these phase 1 studies involving UV1, either as a stand-alone treatment or in combination with the checkpoint inhibitor ipilimumab. Our findings revealed that the immune responses occurred with higher frequency and at a faster rate when UV1 was administered alongside ipilimumab. In all trials, the immune response exhibited remarkable persistence, lasting for several years and displaying substantial fluctuations. Notably, these fluctuations often correlated with clinical events, such as the initiation of new checkpoint inhibitors. Our research also demonstrated that patients who exhibited immune responses experienced prolonged survival compared to those who did not. In our investigations, we examined the expression of the vaccine's target, telomerase, by analyzing tissue samples from patients' tumors. We also examined the infiltration of immune cells before and after treatment, shedding light on their role in the immune response. Our latest study with UV1 focused on its combination with another immunotherapy, pembrolizumab, involving 30 patients with malignant melanoma. This combined treatment proved to be safe for patients and exhibited promising efficacy, even among those for whom reduced responsiveness to immunotherapy would typically be expected.
Additional information
Contact the research support staff.