Prescient Therapeutics Ltd (ASX:PTX) has inked a strategic collaboration agreement with the largest cancer centre in the US, The University of Texas MD Anderson Cancer Center, to create best-in-class, adaptable CAR-T cell therapies to treat blood cancers.
The agreement is designed to combine Prescient’s OmniCAR modular ‘plug and play’ CAR platform with an undisclosed, proprietary binder discovered by MD Anderson’s ECLIPSE (coEvolution of Leukemia and Immunity Post Stem cEll transplant) platform.
ECLIPSE has established a broad sample library, enabling research to uncover unique binders that may allow for targeting blood cancer cells in a manner that is distinct to CAR-T therapies.
These binders are T cell receptor (TCR)-like antibodies which find cancer cells in a similar immune matching mechanism as is used during organ donor matching for transplantation.
Prescient managing director and CEO Steven Yatomi-Clarke said: "Prescient is delighted to enter this strategic partnership with MD Anderson. We believe that OmniCAR is a transformational platform for cellular immunotherapy and we look forward to testing the potential of this promising TCR-like binder for blood cancers.
“Adding this TCR-like binder to Prescient’s armament changes the game by now being able to also target aberrant proteins inside the cancer cell that have been brought to the cell surface.
“The 'plug and play' nature of the OmniCAR platform enables this TCR-like binder to be used in conjunction with OmniCAR’s existing binders, depending on the antigen profile of the patient.
"These are the first important steps in creating a cell therapy ecosystem with OmniCAR at its heart, being adapted to match the antigen profile of individual patients.”
Binding benefits
Using TCR-like binders has several benefits. In this case, it is their ability to target proteins that are usually on the inside of a tumour cell, as distinct from antigens present on the surface of tumour cells.
As such they open up a new range of options for cellular therapy targets.
TCR-like binders are expected to be highly specific, with no expected cross-reactivity to healthy tissues, which is important for safety. This will be especially important when targeting cancer cells that do not express appreciable levels of tumour-associated antigens on their surface.
Multi-arming OmniCAR-T cells with PTX binders against tumour-associated antigens (like its CD33 and CLL1 binders) as well as novel TCR-like binders that target cancer cells using immune matching mechanisms, has the potential to result in synergies including increased efficacy and a broader spectrum of cancer killing.
OmniCAR continues to be at the forefront of cellular immunotherapy, with modular, controllable cell therapies that target proteins on the surface, and now, inside cancer cells.
Collaboration focus
The collaboration between PTX and Anderson will focus initially on a binder to an undisclosed target present on leukemic blasts and leukaemic stem cells, whose expression correlates strongly with poor outcomes.
Notably, this binder does not recognise healthy bone marrow, thereby potentially affording a unique combination of efficacy and safety. OmniCAR cells and binders will be manufactured and tested by the ECLIPSE team headed by Jeffrey Molldrem, MD, professor and chair ad interim of Hematopoietic Biology and Malignancy at MD Anderson.
The costs will be shared equally between the two along with ownership of the resultant therapeutic product.
Prescient’s senior vice president of Scientific Affairs Dr Rebecca Lim said: “A key challenge in developing effective cancer therapies is identifying targets on the surface of these tumour cells, and then being able to bind to these targets.
"This is where the ECLIPSE platform has yielded some valuable breakthroughs in target identification and creating unique binders to these novel targets – targets that until now have been hidden inside the cancer cells.
“An additional challenge in treating most cancers is the heterogeneity of the antigen expression and the fact that these change over time.
"This is where the power of the OmniCAR platform comes to the fore. OmniCAR enables novel TCR-like binders to be uniquely combined with Prescient’s binders, to result in a multi-valent and controllable cell therapy capable of addressing a much broader array of blood cancer cells in order to get the best chance of optimal patient outcomes.
"Furthermore, it enables multiple targets to be addressed over time if the patient happens to relapse.”