Zona Pellucida (ZP), a cancer immunotherapy, is in pre-clinical phase. ZP3 immunotherapy can be applied to ovarian cancer, prostate cancer, (non-small cell lung) cancer and other ZP3 expressing cancers. In October 2014, the ovarian cancer application of ZP3 active immunisation has been exclusively licensed out to HRA Pharma in France. All other applications have been retained by Pantarhei Oncology (PRO).
PRO is looking for partners to ensure continued development of the ZP3 immunotherapy for active and/or passive immunisation for all cancer applications. Two most recent patents are filed in August 2009 (prostate cancer [PC]) and October 2017 (lung cancer [LuCa]), so the project is patent protected until 2020 (PC) and 2037 (LuCa).
The Zona Pellucida 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 tumours 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 tumour 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 Since earlier unpublished research has shown that ZP3 is the strongest immunogen, the treatment concept is focused on active and passive immunisation against the ZP3 antigen.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 tumour 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 tumours as well as reducing the size of existing tumours and preventing the occurrence of metastases.
HRA has performed further pre-clinical studies with positive results on immunogenicity response (ZP3 antibody responses, TCD4/TCD8 responses and signs of apoptosis/necrosis) and adjuvant selection. In a mice model with ZP3 expressing tumours, tumour growth was inhibited with strong TCD8 responses. HRA will not continue into clinical development due to a strategic refocus of the company.