Clinical stage oncology company Prescient Therapeutics (ASX: PTX) has unveiled a novel adjuvant/neoadjuvant named CellPryme-A.
CellPryme-A is designed to be administered to cancer patients as an intravenous infusion in combination with cellular immunotherapy, such as CAR-T cell therapy, to address the hostile tumour microenvironment that cellular immunotherapies face.
In animal models CellPryme-A reduces the number of suppressive regulatory T cells surrounding solid tumours that counteract the effectiveness of CAR-T and other cancer therapies.
Whilst CellPryme- A demonstrated superior tumour killing and survival in pre-clinical studies, its effects were even greater when used together with Prescient’s CAR-T manufacturing technology, CellPryme-M. This exciting new data was presented at the 7th Annual CAR-TCR Summit (Boston, MA), the world’s pre- eminent forum in the CAR and TCR fields of cellular immunotherapy.
CellPryme-A is now ready for clinical testing and can be incorporated into clinical studies of existing cell therapies. For Prescient this opens up another avenue for collaboration with external parties and potential commercialisation.
CellPryme-A has been developed by Prescient in collaboration with the Peter MacCallum Cancer Centre (Peter Mac), with Prescient owning the resultant intellectual property, which is the subject of a patent application.
What is CellPryme-A?
CellPryme-A is an adjuvant/neoadjuvant that is envisaged to be administered to patients as an intravenous infusion either prior to, or shortly after commencing cellular immunotherapy, such as CAR-T cell therapy.
CellPryme-A could be given either before or alongside the cellular immunotherapy. The objective of CellPryme-A administration is to counteract the hostile “cold” tumour microenvironment that is known to dampen the tumour killing ability of CAR-T cells and similar types of cellular therapy.
This is achieved by reducing the numbers of suppressive regulatory T cells (Tregs) that infiltrate into the tumour. Tregs are some of the most immunosuppressive immune cells in the body. In autoimmune diseases, it is the loss or dysfunction of Tregs that results in autoimmunity – where the immune system becomes hyper-activated in the absence of Tregs.
The opposite is true in cancer, where tumours can evade immune surveillance by recruiting Tregs to the tumour. Tregs can create an immunosuppressive environment that prohibits efficient tumour killing, through the release of immunosuppressive cytokines and alterations in metabolic demand.
CellPryme-A reduces the numbers of problematic Tregs in solid tumours
Using an immune-competent mouse model of HER2+ colon cancer (MC38 colon carcinoma) and a conventional HER2-targeting CAR-T cell therapy, twice-weekly administration of CellPryme-A reduced the numbers of Tregs per mg of tumour by two-thirds, after one week of treatment
CellPryme-A significantly increases CAR-T cell penetration into tumours
CellPryme-A increased in CAR-T infiltration into the tumours. Specifically, there was a three-fold increase in CD4+ helper CAR-T cell and a four-fold increase in CD8+ cytotoxic CAR-T cells. These changes were not associated with changes to the CAR-T phenotype. CellPryme-A treatment on its own had no impact on T cell exhaustion. This suggests that CellPryme-A could work in synergy with CellPryme-M.