Prescient Therapeutics Limited building LEGO-like solutions to address rapidly mutating cancers

Melbourne-based oncology company Prescient Therapeutics Limited (ASX: PTX) is using TIA facilities to develop a modular cell-based therapy, like LEGO, to treat cancers which can evade traditional immunotherapies through rapid mutations.

Using their unique covalent modular system named OmniCAR, they aim to build a cell therapy that can be directed toward different tumour antigens by decorating the surface of the T cells with proteins that match specific cancer mutations.

Senior Vice President for Scientific Affairs, Associate Professor Rebecca Lim said the modularity of OmniCAR would be used initially to target specific forms of leukemia, solid tumours and aggressive brain tumours.

It could eventually be expanded for use against other cancers and to treat the same cancers in the same patients if or when the cancers mutate. This is a significant improvement over the current generation of cellular immunotherapies, Dr Lim said.

OmniCAR builds on present CAR T-cell therapies being customised for each individual patient, using their T-cells and re-engineering them through gene-editing to produce the surface proteins called chimeric antigen receptors (CARs).

CAR T-cells. Source: iStock

The CARs recognize and attach to specific proteins, or antigens, on the surface of cancer cells. Revamped T-cells are infused back into the patient, multiply and move around the body, honing in on cancer cells that have the target antigen.

Dr Lim said a small percentage of cancer cells could evade the CAR T-cells, mutate so that they express different tumour proteins on their cell surface, thereby evading the CAR-T cells and result in treatment relapse.

“Treatment relapse is recognised in the research and medical community as an issue that urgently needs to be addressed,” she said.

“CAR T-cells can be hard-wired to go after two or three different antigens, but those two or three antigens are not sufficient to cover all of the tumour, then some cancer cells will remain and the patients face a possible relapse.

“There are many types of cancer that express a multitude of different antigens. Even patients with the same type of cancer – such as acute myeloid leukaemia – can have different antigens and their relapse can look very different.

“Add to that the fact that they have already had previous treatments that could make the cancer respond in different ways from person to person. It is certainly a challenge to address.”

OmniCAR is made up of T-cells joined – like a LEGO attachment – to a targeting compound that seeks out cancer cells with a specific antigen, Dr Lim said.

“It’s a modular system that you can attach new targeting compounds to,” she said.

“OmniCAR can chase cancer cells and if there is treatment relapse, you don’t need to add more T-cells – they’re already in the patient.

“You just infuse a new targeting compound that clicks into the T-cell and has the correct architecture to target the mutated cancer cells.”

Working as Senior Vice President, Scientific Affairs for clinical stage oncology company Prescient Therapeutics, Dr Lim is part of team successful in securing TIA support to access National Biologics Facility (NBF), Queensland Node.

NBF facilities and expertise will be used to produce OmniCAR constructs that will then be sent for third-party assessment for immunogenicity and toxicity. This work is being performed as part of the regulatory approval process for human clinical testing.

TIA supported access to NBF through its Pipeline Accelerator scheme in July, as part of an investment of almost $500,000 to enable 15 researcher and industry projects to access a range of specialist Australian translational medical research infrastructure.

The scheme also supported Dr Lim in her role as Research Group Head at Hudson Institute of Medical Research, providing access to TIA’s Q-Gen Cell Therapeutics for a project in ischemic stroke.