POLE EC pilot study: Identification of neo-antigen specific immunity in POLE-mutant endometrial cancer

In 2013, a new molecular classification of endometrial cancers was proposed.
One of the novel subgroups defined in this molecular classification comprises
patients harboring a somatic mutation in the exonuclease domain of POLE. These
POLE mutated ECs have been characterized as having an ultramutated phenotype
and are associated with a favorable clinical outcome compared to other
molecular subgroups.

Recently, we, and others, have demonstrated high numbers of predicted
immunogenic mutations and enhanced anti-tumor immune responses in ultramutated
POLE-mutant ECs; data which may provide insight into the favorable survival of
this group of patients. A logical next step in understanding the differences in
immune responses between the four molecular subgroups in EC would therefore be
the direct identification and quantification of tumor-specific T-cells
targeting neo-antigens within POLE-mutant endometrial cancer.

The purpose of this project is to investigate the presence and course of
neo-antigen specific immunity in patients with polymerase epsilon (POLE)
mutated endometrial cancer, with the intent to exploit the obtained knowledge
of neo-antigen specific immunity for the development of neo-antigen specific
adoptive T-cell transfer therapy for this disease entity.

Pilot study

The risk of participation is considered minimal, as participation consists of a
venepuncture. Patients will not benefit from participation in the study. The
ultimate goal of this study is to develop immunotherapy for endometrial cancer
in order to improve disease free survival and reduce the need for other
adjuvant therapies such as radiation and chemotherapy in a selected group of
patients. To this end it is necessary to gain further insight into natural
immune responses to specific tumour neo-antigens in POLE-mutated endometrial
cancer patients.