Zona Pellucida for cancer immunotherapy
The Zona Pellucida (ZP) is a glycoprotein matrix layer around the oocytes (egg cells) in the ovary, that plays an essential role in fertilisation and implantation of an embryo. The human ZP layer contains four different immunogenic glycoproteins (ZP1-4), that are specific for the ovary and do not occur anywhere else in the female or male body, implying potential safety (no cross-reactivity) when ZP is used as immune target.
In collaboration with the Institute of Biomedicine at the University of Turku, Finland, Pantarhei has discovered that some malignant tumors such as ovarian cancer, prostate cancer and (non-small cell) lung cancer express ZP3 antigens abundantly in 60-90% of the cases in the primary tumor as well as in metastases. This makes ZP3 is interesting target for immunotherapy in different types of epithelial cancers.
Based on these findings, Pantarhei has patent protected the potential use of ZP antigens for the treatment of ZP expressing cancers. Since earlier unpublished research has shown that ZP3 is the strongest immunogen, the treatment concept is focused on active and passive immunisation against the ZP3 antigen. The demonstration of expression of ZP3 by a tumor is a biomarker for treatment.
Proof of principle of ZP3 immunotherapy was obtained in a transgenic animal mouse model for granulosa cell ovarian cancer. A mixed humoral/cellular response was demonstrated preventing the formation of tumors as well as reducing the size of existing tumors and preventing the occurrence of metastasis.
In October 2014, the ovarian cancer application of ZP3 (passive) immunisation has been exclusively licensed-out to HRA Pharma in France. All other applications, including those for advanced and metastatic prostate cancer, non-small cell lung cancer and other ZP3 expressing cancers have been retained by PRO. Preclinical studies are in progress for the active immunisation route by HRA Pharma with positive results. PRO is looking for partners to develop ZP3 immunotherapy for active and/or passive immunisation for the other cancer applications.