Digital public defence: Astri Fjelde Maaland
MSc Astri Fjelde Maaland at Institute of Clinical medicine will be defending the thesis "Development of next generation radioimmunotherapies of non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia" for the degree of PhD (Philosophiae Doctor).
Photo: Mick Tully, Image Communication
The public defence will be held as a video conference over Zoom.
The digital defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital trial lecture - time and place
- First opponent: Professor Annemiek van Spriel, Radboud University Medical Center, the Netherlands
- Second opponent: Researcher Sture Lindegren, Sahlgrenska Academy, University of Gothenburg, Sweden
- Third member and chair of the evaluation committee: Professor Ludvig Munthe, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor II Karl-Johan Malmberg, Institute of Clinical Medcine, University of Oslo
Head physician Arne Kolstad, Department of Oncology, Oslo University Hospital
Patients with non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL) are treated with chemotherapy and anti-CD20 antibodies or small molecule inhibitors. These regimens are initially effective in inducing responses, but most patients relapse or become refractory to the treatments. New treatments with different targets and mechanisms of actions are needed.
The aim of the thesis was to study the effect and safety of two radioimmunotherapies (RITs), in preclinical models of NHL and CLL. RIT combines antibodies with radionuclides. The antibody facilitates the specific targeting of the cancer cells so that the cytotoxic radiation from the radionuclide reaches the cancer cells, leading to an increased dose to cancer cells while sparing the surrounding tissue.
The RIT 177Lu-NNV003 emits beta radiation and is more suitable to treat bulky diseases like NHL. The radiation is long-ranged and can harm cells in clusters even though 177Lu-NNV003 is not bound to all of them. 212Pb-NNV003 emits alpha radiation, which is short-ranged but more cytotoxic. Thus, it is more suitable to treat a disseminated disease like CLL. 177Lu-NNV003 showed a good anti-tumour effect in intravenous mouse models, representing disseminated disease, and subcutaneous mouse models, representing bulky disease. The anti-tumour effect of 212Pb-NNV003 was superior to that of 177Lu-NNV003 in similar intravenous models.
To increase the effect of 177Lu-NNV003 it was combined with olaparib, an inhibitor of PARP, an enzyme responsible for repairing DNA single-strand breaks. When inhibited, the single-strand breaks remain unrepaired and progress into lethal double-strand breaks. By combining the RIT with olaparib, the single-strand breaks made by 177Lu-NNV003 will become double-strand breaks, thus becoming more cytotoxic. The combination was studied in seven NHL cell lines, and was found to be clearly synergistic in four of the cell lines and tended towards synergistic in two more.
contact the Research Support staff