Australia is handicapped in the delivery of cell therapies, says Alan Trounson

THE promise is remarkable: a new class of affordable, effective cancer treatments beyond surgery, chemotherapy, biologicals and radiation. Imagine cancer specialists being able to select from a range of treatments to supercharge a patient’s immune system, helping it eliminate cancer.

This is not a distant vision. It is happening right here, right now. A research team, including Cartherics Pty Ltd, has a major Federal Government grant to develop such ‘off-the-shelf’ immunotherapies to fight aggressive forms of cancers like relapsed ovarian and gastric cancers.

Currently, selected immune therapies are available overseas. But they must be developed for each patient at a cost of roughly $500,000 per treatment. In contrast, the off-the-shelf approach, which combines stem cells and immunotherapy, could save considerable costs to the healthcare system and time for patients.

Cartherics is not alone. Nationwide, teams are developing cell therapies for use in treating Parkinson’s disease, diabetes, spinal cord injury, blindness, heart disease and cancer.

Unfortunately, there is a hitch. Government support is insufficient to take advances from the laboratory to the market place. Yet perversely, there is lack of acceptance that commercialisation of medical research is essential to enable the investment of the quantum of funds needed to bring these advances to patients in desperate need.

This conundrum plays out in cell therapy research because scientists need just that: cells. They require donated human cells to run experiments. In Australia, most such donor cells are available frompublic cell banks, specifically umbilical cord blood and bone marrow banks. But the cells the blood or marrow contain are available only for research purposes and must be destroyed when the project ends. Without the donor cells there can be no products.

And without the prospect of products rolling off the production line, there is no reason for biomedical companies to invest in the research. Private sector investment is critical to the innovation process. Government grants are insufficient to take advances from the laboratory to the market where they are available to patients in desperate need.

Our group’s experience is a case in point. In order to develop our products, we need access to so-called human leukocyte antigen (HLA) compatible donor blood. We then convert donor blood cells into ‘induced pluripotent stem cells’ (iPSCs) from which they produce a large bank of specialized cancer-killing immune cells, or chimeric antigen receptor T-lymphocytecells. These CAR-T cells form the core of our off-the-shelf immunotherapies.

We planned to collect blood from suitable donors through the Peter MacCallum Cancer Centre hospital, so made an ethics submission to the centre’s human research ethics committee (HREC). We received approval to conduct the study.

In order to try and identify suitable donors and request their participation, the team approached the Australian Bone Marrow Donor Registry (ABMDR) and was encouraged to submit a research proposal to its HREC.  Initially, the request was for ABMDR to enquire of its few rare donors – those with so-called major human leukocyte antigen genotypes which are compatible with tens of thousands of Australian cancer patients – if they would consent to providing a blood sample for making iPSCs which can be infinitely expanded to make cells for therapeutic purposes. The Ethics Committee response was:

“Our current understanding of your project is that you cannot isolate the research and future commercialization components, and therefore you would need approval for commercialization of cell lines and biobanking prior to commencing. The ABMDR board has reviewed the issue of commercialization of material derived from ABMDR donors and affirmed that this is not permitted. Therefore, the ABMDR is not is a position to support your application as it stands.”

Further, the HREC took the position that, while it could support the project for research purposes only, the donor cells, as noted earlier, would have to be destroyed once the research was completed. That would have been a complete waste of time and resources.

While I acknowledged that the existing banked bone marrow or blood samples are only consented for research that does not involve commercialisation, the existing samples were irrelevant to the proposed project.  All that was requested from ABDMR was to be able to contact suitable donors to ask if they would be willing to participate in the project.

It seems unreasonable that donors could not be asked to donate their own blood for research that may have a major benefit for thousands of patients with cancer or other diseases. Surely, it is the donors right to decide whether or not to provide consent to donate blood and allow commercialisation of any products that might result from the research. In my experience, bone marrow donors generally have high motivation for providing therapeutic benefit to others.

Where does this leave Australian research in cell therapies like those conducted by our group? Presently the only prospect is to try and obtain these appropriately consented blood samples internationally. Public cell banks in many overseas countries will sell cord blood or peripheral blood from these unique donors for research, including consent to commercialise any products that are developed.

Large-scale US, European, Japanese, Korean and Chinese research teams are not hampered by the difficulties faced by Australian teams. Consequently, cell therapies are beginning to emerge overseas for many applications. Without access to donors for such work, Australian teams – and ultimately patients – will be at a considerable disadvantage.

I encourage those responsible for creating or implementing such rules that prevent these very special donors being asked if they are willing to provide a blood sample for generating a commercial product that may save millions of lives, to reflect on the problem – and the solution: a simple consent process for donors to registries. It only makes sense.

Alan Trounson is Emeritus Professor at Monash University, Distinguished Scientist with the Hudson Institute of Medical Research, and CEO Cartherics Pty. Ltd.