Product pipeline: Ovarian Cancer

Epithelial ovarian cancer is the most common cause of death from gynecological malignancies and accounts for 5% of all cancer deaths. Its non-specific clinical presentation and absence of effective screening methods are responsible for the 70% of patients who present with an advanced stage of disease at the time of diagnosis.

Primary treatment for advanced stage ovarian cancer consists of cytoreductive surgery followed by platinum/paclitaxel based chemotherapy. When residual or recurrent disease manifests itself, resistance to chemotherapy often prohibits further curative therapy, resulting in an overall survival for patients with advanced stage ovarian disease of only 10-20%.

So far, efforts to improve survival among women with advanced ovarian cancer have had only limited success. To improve this poor outcome for ovarian cancer, patient studies focus either on the addition of targeted or biologic agents to first line chemotherapy or their application as maintenance or consolidation therapy for patients with microscopic or subclinical residual disease after first line treatment.

Research during the last decade has revealed that ovarian cancer patients exhibit significant immune responses against the tumor. An attractive tumor specific antigen to be recognized by T cells in ovarian cancer is the frequently over-expressed (40-50%) and mutated p53 protein. In cancer cells loss of wild-type p53 function e.g. by p53 mutations may lead to more aggressive tumor growth, failure to respond to standard therapy and poor prognosis. Different expression levels of p53 in tumor cells compared to normal cells provide an immunological window for p53 wild-type (wt) specific immune effector cells. In other words, different expression levels of p53 in tumor cells results in different numbers of wt-p53 derived T cell epitopes in MHC molecules and possibly also in other epitopes compared to normal cells, providing T cells the immunological window to discriminate between tumor cells and normal cells. Mutant and wild-type p53 specific CTL have been described in mice.

Through ISA's approach, using synthetic long peptides encoding the p53 protein itself instead of short MHC binding peptides, p53-specific CTL and Th responses against dominant and cryptic MHC class I and II peptides will be induced that are not limited by the HLA type of the patient.