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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Karine Breckpot, Vrije Universiteit Brussel, Belgium
- Second opponent: Lecturer Mike Bogetofte Barnkob, Odense University Hospital, Denmark
- Third member and chair of the evaluation committee: Professor II Morten C. Moe, University of Oslo
Chair of the Defence
Associate Professor Tor Erik Rusten, University of Oslo
Principal Supervisor
Senior Scientist Sébastien Wälchli, Oslo University Hospital
Summary
Immunotherapy consists in the use of patient’s own immune system to treat cancer. One strategy relies on the modification of specialized immune cells, T cells, with a molecule called Chimeric antigen receptor (CAR). CARs are artificial proteins able to recognize antigens presented on the surface of cancer cells and stimulate T cells. Thus, CAR expressing T cells acquire the ability to kill cancer cells.
CAR T cell therapy has showed unprecedented clinical benefit for blood malignancies with complete remissions in patients with cancers resistant to conventional treatments. Nevertheless, some patients relapse due to antigen loss. So far, CAR therapy has shown limited clinical efficacy against solid malignancies. The present thesis focuses on the development of CAR targeted against alternative antigens. More specifically, we have rehabilitated a CAR-dismissed target and developed CAR against an emerging class of cancer markers, namely tumor-associated carbohydrate antigens (TACAs). Several in vitro and in vivo methods were used to assess three novel CARs, each reported in individual research papers.
The first paper demonstrates the potential of targeting CA125 for treatment of ovarian cancers. The second paper describes a novel target from the emerging category of cancer-specific sugars, CD75s, as a suitable target for combinatorial CAR treatment approaches against lymphoma. In the third paper, we generated a novel monoclonal antibody with unique specificity, AM52.1, targeting an aberrant glycosylation shared among several solid cancers. We designed an AM52.1CAR construct and demonstrated its pre-clinical efficacy.
The thesis demonstrates that alternative CAR targets beyond the frequently exploited ones, notably TACAs, can be developed and display strong potential for clinical implementation.
Additional information
Contact the research support staff.