Identification and characterisation of novel antigens for the immunotherapy of ovarian cancer

Ovarian cancer is the fourth most common cancer in the UK, affecting approximately 6,500 women each year. It can occur at any age but is most common after menopause. Although the chances of developing ovarian cancer are increased in those with close relatives who have been affected, most individuals have no family history. Survival in patients with ovarian cancer varies with stage but on average 5 year survival is 48%. Most patients are diagnosed with stage I (30%) or stage III (40%) disease with 5 year survival rates of 90% and 20% respectively. Only 4% of all ovarian cancer patients are diagnosed with stage II (5 year survival is 50%) and 15% with stage IV (5 year survival is 6%).

Diagnosis at an early stage (I or II) can greatly improve the chances of effective treatment for ovarian cancer patients however diagnosis tends to be in the later stages of disease (III and IV) when patients present with pelvic or abdominal pain, urinary frequency or urgency, increased abdominal size or bloating. This diagnosis is confirmed by a pelvic examination, transvaginal ultrasonography and detection of carbohydrate antigen 125 (CA125) in the tumour tissue. However CA125 has proven to have poor specificity for ovarian cancer with variable expression between patients (recently reviewed in (1)). CA125 appears to work better as part of a panel to improve specificity, sensitivity (100%) and differentiation of ovarian cancer from endometriosis (2, 3).

Our group wish to identify novel targets for the immunotherapy of ovarian cancer. One of the most effective ways to screen for antigens is SEREX (serological analysis of recombinant cDNA expression libraries), which was first described in 1995 by Sahin et al (4) and has few limitations with regards to patient material. This technique identifies tumor antigens based on their recognition by antibodies in patient sera and has been used to identify >2,000 tumor antigens in a diverse range of malignancies (www2.licr.org/Cancer ImmunomeDB/).

To do this we will immunoscreen a cDNA library with sera from patients with early stage ovarian cancer at disease presentation. We want to identify cancer-testis antigens (CTAs) if possible. These proteins have restricted expression, being found in tumour tissue and in a limited number of healthy tissues at low levels. Therefore targeting CT antigens with immunotherapy should not lead to catastrophic auto-immune responses against healthy tissue (5). The project will involve the use of a range of techniques including patient sample processing, immunoscreening, manipulation of bacteria, tissue culture and gene expression analysis (sequencing, RQ-PCR, immunohistochemistry and flow cytometry).

We are looking for a motivated and enthusiastic individual who can work well in a busy team. The project relies on someone who is able to interact with clinicians and scientists and will provide an important link between the School of Life Sciences at the University of Hull and our colleagues in the Hull York Medical School and Castle Hill Hospital.