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Adjudication committee
- First opponent: Senior Consultant Christian Kersten, Hospital of Southern Norway
- Second opponent: Senior Lecturer Patricia Lalor, University of Birmingham
- Third member and chair of the evaluation committee: Associate Professor Are Martin Holm, University of Oslo
Principal supervisor
Professor Pål Dag Line, University of Oslo
Summary
Oncolytic immunotherapy shows promise in early stages
Primary liver cancer is a malignant disease characterized by few treatment options. Surgical resection and transplantation are the only curative options, but require relatively small and easily accessible tumors. A new type of treatment using oncolytic molecules or compounds shows promise in early stages.
The aims of the thesis were to investigate the therapeutic efficacy a new generation of oncolytic compounds in preclinical animal tumor models. The oncolytic compounds, which falls into the category of immunotherapy, are designed to be administered directly into solid tumors where they rapidly kill cancer cells and provoke acute inflammation.
Several oncolytic compounds were found to exert potent therapeutic activity in various preclinical models as seen by complete tumor regression. Additionally, all drug candidates were capable of inducing immunogenic cancer cell death, a type of cell death known to promote immune responses against the tumor. One compound in particular, named LTX-401 (developed by Lytix Biopharma, Oslo), demonstrated potent efficacy in rats having an aggressive form of liver cancer.
Upon intratumoral injection, the tumors collapsed within few days and cured the majority of animals. Cured animals were also resistant against relapse of the tumor, hence indicating that the treatment had stimulated the body’s immune system to remember and recognize the cancer cells. Additionally, LTX-401 had a favorable toxicity profile as it displayed no side effects.
Overall, the study shows that local treatment with oncolytic compounds is a feasible and effective way to treat cancer, and may represent a ‘next-generation cancer immunotherapy’ in patients with primary liver cancer.
Additional information
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