Therapeutic antibody development company Patrys Limited (ASX: PAB) has made a technical breakthrough with the selection of an optimised stable cell line for its lead asset PAT-DX1 and the fight against cancer.
The company said this important step allows the company to establish large- scale production of PAT-DX1 deoxymab for final preclinical studies, first-in-man studies, and partnering activities.
The establishment of a stable, PAT-DX1-producing cell line by Patrys is the culmination of a manufacturing development and optimisation programme that was initiated in mid-2019. The development programme included modification of PAT-DX1’s protein back-bone to improve its properties for use in human therapeutic applications.
Cell lines expressing the modified PAT-DX1 were developed and an extensive selection processes was conducted to identify single, clonal cell lines that produced high yields of high-quality PAT-DX1. The final step was to ensure that the cell line was stable and able to deliver reproducible and consistent production of PAT-DX1 protein over time.
Over the past months Patrys evaluated six different optimised cell lines and has selected a best performer from these studies. The cell line that has been selected will be stored as a Master Cell Bank (MCB) which will form the basis for all future production of PAT-DX1.
The selection of a stable cell line for producing PAT-DX1 means that all future studies undertaken by either Patrys or its partners and collaborators can be based on suitably qualified product, including supporting ongoing research effort being conducted around the globe on this technology.
Having a consistent and qualified product means that data can potentially be leveraged from a broad range of studies covering applications such as therapeutics, nanoparticle drug delivery, antibody-drug conjugation and diagnostic imaging agents.
Patrys’ deoxymab platform is based on the deoxymab 3E10 antibody that was first identified as an autoantibody in a mouse model of the human disease systemic lupus erythematosus (SLE). While most antibodies bind to cell surface markers, deoxymab 3E10 penetrates into the cell nuclei and binds directly to DNA where it inhibits DNA repair processes.
Cancer cells often have high levels of mutations and underlying deficiencies in the DNA repair mechanisms. For these reasons, the additional inhibition of the DNA repair processes by deoxymab 3E10 can kill cancer cells, but appears to have little impact on normal cells.
As a single agent, deoxymab 3E10 has been shown to significantly enhance the efficacy of both chemo- and radiotherapies. Further, deoxymab 3E10 can be conjugated to nanoparticles to target delivery of chemotherapeutics and imaging agents to tumours.
Patrys has developed two humanised forms of deoxymab 3E10, both which have improved activity over the original deoxymab 3E10 antibody. PAT-DX1 is a dimer (two joined subunits) of the short chain from the binding domain of deoxymab 3E10, while PAT-DX3 is a full-sized IgG antibody. In a range of pre-clinical studies, PAT-DX1 has shown significant ability to kill cancer cells in cell models, human tumour explants, xenograft and orthotopic models.
PAT-DX1 has been shown to cross the blood brain barrier, reduce tumour size, and increase survival in multiple animal models of brain cancer, other cancers, and cancer metastases. PAT-DX1 is tumour-agnostic, meaning that it can target many different tumour types in the body, regardless of specific tumour antigens. Patrys believes that PAT- DX1 may have application across a wide range of cancers including gliomas, melanomas, prostate, breast, pancreatic and ovarian cancers.
Deoxymabs, such as PAT-DX1 and PAT-DX3, can be used to target nanoparticles carrying a payload of anti-cancer drugs specifically to tumours. This allows specific delivery of cancer drugs to multiple types of cancer while having minimal impact on normal, healthy cells.