CureTalks recently featured eminent immunologist and CAR-T cell therapy exponent Dr. Carl June of University of Pennsylvania. Dr. June discussed in detail his research journey and therapy under discussion. The basic idea of T-cell therapy is to remove a patient’s white blood cells and then add a molecule to the cells which can stick onto cancer cells, lock-and-key style. The cells are then returned to the patient. The patient panel consisting of Gary Petersen, Jack Aiello and Mike Scott discussed side effects, tumor receptors, gene therapy using HIV, effect on solid tumors, ongoing research on CAR-T cells and more. Listen to the talk HERE.
An excerpt from the show where Dr. June shares some special moments from his CAR-T cell research journey. (12:10)
You know we started off first, with just, what we were doing really is kind of CAR-T cell therapy – it is a new form of transfusion medicine. So, the first successful transfusions in animals were blood cells. For that to happen, they had to develop the typing of the blood system – so called ABO antigens – to find out who could be a blood donor and so on. Now what we are doing really is T cells – you know, because CAR-T cells are formal blood cells. We are doing T cell infusions. So, our first “Eureka” was when we actually treated those AIDS patients, we made CAR-T cells for HIV and we gave them a single dose of CAR-T cells. We saw immediately, their T cell counts went up, in many cases they doubled and went to normal levels. That was an evidence that the CAR-T cells could go into the patients and stay, and actually survive, start dividing. So, that was what we were hoping for, and it worked better than we thought it would.
But, in a really curious twist, the FDA has a rule, in the US, that patients treated with gene transfer technologies…So this is a form of gene therapy, because the cells are genetically modified and in this case, the patients got CAR-T cells for their HIV. Starting 1997, the FDA has a rule that each patient needs to be followed up to 15 years and tested each year to make sure that he has been safe, and there has been no toxic effects from the genetic engineering. Analysed in 2012, of all the patients we had treated back in 1997 and 2000, and there were 40 patients, and we analysed them, because the FDA had a rule that if we could show that the gene transfer was had gone away from the patient, then we would no longer have to have the expense of following the patient every year.
So, we analysed all our patients, from the samples in the freezer, and were astonished to find that, in fact, more than a decade later, they were still engrafted and had these CAR-T cells at very stable levels. No one expected that. In the previous trials, that transfused T cells, they had not ever lasted longer than a week. We found that the half life of these T cells is 10 years in patients of HIV. So it suggested for the first time that you can make a living drug, you can genetically modify someone’s T cells and give them back, and it would then be there on patrol for potentially the rest of the patient’s life, so that they can act in a way like a vaccine. So that was the first amazing thing.
And then the second major one was really in 2010 when, when we treated the first patients with these CAR-T cells, this one was called CTL109 or CART19 because it targets…its a CAR-T cell against a molecule called CD19 on leukemia cells. When we treated those patients we did not know what would happen. All previous CAR cell trials in patients in cancer had failed and not shown any effects. We had all three patients show remarkable remissions. It was so unexpected that patient 1, who we reported in New England Journal of Medicine in 2011, patient 1 when the bone marrow biopsy came back with no leukemia – I did not believe it – I said, that basically they must have missed it. leukemia is in the bone marrow, usually they biopsy part of the pelvis, so I just said “biopsy the other side” – and so we did the first biopsy on day 28, and it was negative. And then biopsy on day 31 from the other side came back also normal, with no leukemia! So that was astonishing and we had that repeated many other times.
CAR-T cell therapy is being heralded as the game changing technology for cancer treatment. Listen to the CureTalks on Dr. Carl June’s CAR-T Cell Therapy Journey and the Cancer Treatment Revolution. Don’t miss this one!