What we are doing is just adding some genetic modification of T-cells to make these cells available as an off the shelf product to be able to treat patients in an allogeneic fashion.
Can you tell me what it is normally that is done? Because the cures we’ve seen have been with autologous transfer using the so-called CAR T-cell therapy. What exactly is that and how does it work?
What’s called the autologous adoptive T-cell immunotherapy is clinicians will take the T-cells from the patient, will infect them with a modified virus that will bring a chimeric antigen receptor to the cell and this receptor will recognise a tumour antigen and in that way the cell will kill the tumour cells. So what is happening in this context is the cells come from a patient and they are injected back in the same patient.
How is this approach better for targeting than other methods?
In fact it’s a direct killing of the cells so the modified cells have a high specificity because it has the binding of the main monoclonal antibody and it will perfectly recognise the antigen, bind to the tumour cell and drive the killing of these cells.
There have been some fairly dramatic cures with this therapy but, of course, it’s only been in a handful of patients because you have to make the chimeric antigen receptor T-cell therapy individually each time. So what is it that you’re doing? How could this change?
Our approach is that we have been developing nucleases for several years so these nucleases will recognise a specific gene, cleave it and inactivate the gene. So we have combined this CAR T-cell technology with genome engineering to inactivate, for example, the T-cell receptor and in that way a cell that can be issued from a healthy donor could be modified and treat in an allogeneic fashion many patients. So far we have been efficiently doing this genetic modification, this multiplex genome editing means that we can have some double knockouts of different genes and we have validated the anti-tumoural activity in mouse models.
Could this become an off the shelf drug?
Yes, that’s what we hope. We are planning to do first human tests in 2015 so we are working hard to get it into the clinic.
How effective would these drugs be?
They should be as effective as the autologous T-cell, the advantage is that in a single production run of these CAR T-cells you can treat many different patients.
What types of cancer might you be able to treat?
For the moment everything that has been tested is mostly on haematological cancers and that’s what we are developing but we are now trying to find different genetic modifications that will help us to target tumour solid also.
What would be the first candidates among haematologic cancers?
The first candidates we are working on are, for example, targeting the CD123 antigen in acute myeloid leukaemia patients and also targeting the BCMA gene in patients with multiple myeloma.
What’s the clinical potential of this?
The clinical potential is that you can have an off the shelf therapeutic cellular product that could be infused into patients rapidly. You don’t need to take the patient’s own cells and develop all these modifications which is a long process, an expensive process, that you need to know how to do it. So in this case the cells will be ready to be injected into the patient and it will be much faster than these autologous approaches.
Could this apply to solid tumours at any time?
Yes, we are also working on that so we hope. True, there is more difficulty in treating the solid tumours but we think it can be done, for sure.
What message should doctors take from this work?
The take home message is that we are developing this off the shelf platform that could be easily upscalable and easily modified to target different kinds of tumours. So it’s some technology that should be attentive to it because it will change the way we treat cancer in the future.
What should doctors say to patients in light of these successes?
It’s something that many patients are asking for these kinds of treatments because of what we have seen in the news is amazing, it’s revolutionising the way that people are facing cancer and how you see that it can be done. So patients should be aware of these kinds of technologies and these alternative treatments.
This isn’t available to many people?
No, it’s available for patients that have some T-cells in good condition that will allow the production of CAR expressing T-cells but hopefully if we have an allogeneic product it will be available for many, many people. We are now starting the development of the pre-clinical and clinical studies and we hope to be able to be starting our first human tests in 2015. So once we prove that there is efficiency of this technology, of this approach in treatment of lymphoma, we can move to the other pathologies and still have the process of developing these kinds of products.
