WT1-, PRAME- and MSLN- specific immunity in epithelial ovarian cancer.

Eggink, F.A. (2014) WT1-, PRAME- and MSLN- specific immunity in epithelial ovarian cancer. thesis, Medicine.

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Abstract

Epithelial ovarian cancer is the leading cause of death in gynaecological malignancies. Despite moderate alterations in standard therapy regimens in previous decades, prognosis remains poor: relapse rates of up to 90% have been described. The development of immunotherapy plays an important role in the search for new therapeutic strategies. Several studies have demonstrated the presence and effects of T-cell responses in ovarian cancer. However much less is known about humoral immune responses. This pilot study aimed to optimize and validate the techniques needed to investigate the presence of humoral immune responses (antibodies) against three tumour-associated antigens, namely: Wilms’ Tumour 1 (WT1), Preferentially Expressed Antigen in Melanoma (PRAME), and Mesothelin (MSLN). All are potential targets for the development of immunotherapy. Patients who underwent primary surgery in the UMCG between 1985 and 2007, of whom RNA and/or serum samples were available, were selected for analysis. Tumour expression of PRAME and MSLN was determined using real time-PCR and immunohistochemical staining, respectively. High MSLN expression was found to be an independent negative prognostic factor for disease-specific survival. Subsequently, ELISA assays were developed for antibody detection in patients with confirmed antigen expression. In total 44, 14 and 15 patients were selected for the analysis of WT1-, PRAME-, and MSLN specific immunity, respectively. The presence of specific antibodies in serum was confirmed for all three antigens studied. However, no associations could be demonstrated between the presence of tumour-specific antibodies and clinicopathological patient characteristics or disease-specific survival. This may be attributed to the small number of patients involved in this study. In the near future a new study, using a larger patient population, will be set up. This will allow further optimisation and validation of the ELISA assays. Continuing efforts aimed at analysis of humoral immune responses against these antigens may provide new insights for the development and optimisation of novel therapeutic strategies in ovarian cancer.

Item Type:	Thesis (Thesis)
Supervisor name:	Nijman, Prof. Dr. H.W. and Leffers, Mw. Dr. N. and UMCG
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:54
Last Modified:	25 Jun 2020 10:54
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1444

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