Analysis of the neo-antigen specific T cell response : and consequences for personalized immunotherapy

Author(s):
Buuren, M.M. van
Published
2016
Publication type
Doctoral Thesis

Abstract

Cancer immunotherapy has shown clinical effectiveness over the recent years, especially in patients with a high mutational load in the tumor.

Mutated epitopes, so called 'neo-antigens', are presented on the tumor and can be regarded as foreign by the immune system.

In this thesis, the importance of neo-antigens in the anti-tumor response is explored. First, the characteristics of antigens that can be recognized on human tumors are described, with a specific focus on neo-antigens. Second, technologies are described to systematically analyze neo-antigen specific reactivity in patients with cancer. Third, I show that neo-antigen specific reactivity is a common phenomenon in the CD4 and CD8 T cell compartments of patients with melanoma. Finally, I discuss what the expected value of neo-antigens is in the context of personalized cancer-immunotherapy.

Personalized immunotherapyCancerImmunoeditingpMHC complexNeo-antigensTumor specific mutations
Defense date
2016-06-01
Language
English
Supervisor(s)
Schumacher, Ton N.M.
Advisor(s)
Kesmir, Can
Committee member(s)
Haanen, John B.A.G.; Melief, Kees C.J.M.; Heemskerk, Mirjam H.M.; Ossendorp, Ferry A.; Kuball, Jurgen; Sahin, Ugur
Qualification
Ph.D.
Degree granting institution
Leiden University Medical Center, Medicine, Leiden University, Leiden
hdl
1887/39812
ISBN(s)
9789462332973

Funding

Sponsorship
NKI-AvL