CD19 CAR T-cells effective with with low dose chemotherapy
Dr Stephanie Goff - National Cancer Institute, Bethesda, USA
We’ve been studying the use of what we call a CAR T-cell, or a chimeric antigen receptor T-cell, targeting CD19 which is on the surface of B-cells. We’ve been using our CAR CD19 T-cells against diffuse large B-cell lymphoma which is one of the most aggressive.
Can you tell us more about the T-cells that you’ve been using?
What we do is we take T-cells from a patient, a blood sample from a patient, and we genetically engineer them to have a receptor that recognises CD19. We call this a chimeric antigen receptor because on the outside it can see something like an antibody does but on the inside it signals like a T-cell.
How has this been responding to people with the low dose chemotherapy?
We published a trial in this about a year ago where we used high dose chemotherapy. So a lot of people said maybe it’s just the chemotherapy that you’re giving that’s affecting the lymphoma and not your cells. So we tried to do it with low dose chemotherapy. We treated 22 patients with advanced lymphoma, 19 of those had diffuse large B-cell lymphoma. In that group we had 12 responders, 9 of those were in the diffuse large B-cell group, the other 3 were patients with follicular lymphoma or mantle cell lymphoma.
Were there any other associated markers with their response?
We’ve studied a number of things and it’s difficult to say. We do know that IL-10 and IL-15 are two proteins that are elevated in patients who are responding. One of the things that we are seeing when we give these cells is that our patients tend to develop what we call neurotoxicities which can range from anything from a mild confusion to difficulty finding words to an inability to speak. These are all very transient and they go away within two weeks.
So compared to the high dose chemotherapy that you were initially trialling this against, how does this stack up overall as efficacy, as safety, as potential for further treatment?
By demonstrating the use of these cells with low dose chemotherapy we’ve been able to show definitively that it’s not the chemotherapy that’s affecting the lymphoma, it’s our T-cells that are doing the trick. What we see as far as the toxicities with the neurotoxicity, it’s reversible, it can be treated and the patients aren’t experiencing any long-term problems. All of our patients that have CRs in the diffuse large B-cell population, they’re all ongoing, anywhere from 6-20 months so we think when we can make all of the lymphoma go away it’s a durable response.
How do you see this influencing the standard of care for people with these lymphomas in the future?
Obviously we did a very small single arm study but as larger multicentre, multinational trials get started CD19 therapy with CAR is going to be one of the next treatments for patients with refractory lymphoma.
Are there any trials by name or by number that you know at the moment that you can report?
I know that our research collaborative partner, Kite Pharma, has a programme going now with a product called KTE-C19. That’s going in the States and getting ready to start in Europe soon.