The trial lecture will be held as a video conference over Zoom.
The digital trial lecture 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.
Click here to participate in the public defence
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Professor Pierluigi Porcu, Thomas Jefferson University
- Second opponent: Group Leader Sofia Frost, Roche Glycart AG
- Third member and chair of the evaluation committee: Researcher Lise Kveberg, University of Oslo
Chair of the Defence
Professor Kristin Austlid Taskén, University of Oslo
Principal Supervisor
Research Manager Ada Repetto-Llamazares, Nordic Nanovector
Summary
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Patients with non- Hodgkin lymphoma (NHL) are often treated with the combination of chemotherapy and CD20 targeting immunotherapy. However, some of these patients develop relapsed or refractory disease after initial treatment. For these patients, it is important to find alternative treatment schedules that are effective. The focus of the thesis was to investigate the preclinical therapeutic potential of combining radioimmunotherapy (RIT) with immunotherapy and small molecule inhibitors with the aim of improving therapeutic outcomes in NHL. RIT consists of monoclonal antibodies (mAb) paired with radionuclides to selectively deliver cytotoxic radiation doses to the antibody target-specific cells. The radioimmunoconjugates (RIC) Betalutin® and Humalutin consisting of murine and chimeric mAb respectively were used. These mAbs are linked to the chelator DOTA that chelates the beta-emitting radionuclide lutetium-177. The RICs bind to CD37 proteins expressed on NHL cell surfaces and irradiate the cells inducing DNA-damage and subsequent cell death. The chimerization of Humalutin enables it to also work as an immunotherapy, modulating an immune response against tumour cells. Betalutin® was evaluated in combination with rituximab, a CD20-targeting immunotherapy that activates immune cells to attack and decimate the tumour cells. The combination resulted in synergistic therapeutic effects in both rituximab-responding and rituximab-resistant NHL animal models. The combination of Humalutin and Olaparib, a small molecule inhibitor that inhibits the PARP enzyme whose function is to repair DNA single strand break (SSB) was explored. Inhibited repair of SSB in combination with radiation-induced DNA damage results in fatal irreparable DNA double strand breaks. The combination resulted in synergistic effects in NHL cells. The results indicate the potential clinical benefit of combining Betalutin with CD20 targeting immunotherapy as well as combining Humalutin with PARP inhibitors. |
Additional information
Contact the research support staff.