The Miracle Cure? Kite Pharma and the Immunotherapy Revolution

An Interview with Arie Belldegrun

What we are doing is giving one single infusion to the patient. And that's the difference. We are not giving a treatment for life. These cells are long-lived. They live as long as you do. They have memory and they don't lose their specificity. So if the cancer starts growing, they immediately come after the cells and kill them even six months later.

OR: It sounds as though there really shouldn't be side effects to this treatment.

Belldegrun: Yes and no. These cells are not attacking normal cells. They are not going to create hair loss. But they are melting tumors within weeks. Where is all the debris going? Into the blood. And it can take time till it is cleared from the body. So you have what's called cytokine release syndrome. Therefore, in the first two weeks, you have side effects. But after two weeks, all of that disappears. Patients don't need anything else. The longest we have now alive is over five years. And these are patients that, barring our treatment, could not have lived more than six months.

OR: Why does it work on some people and not others?

Belldegrun: Very good question. We need more patients to understand why. So far – see January's issue of the Journal of Clinical Oncology -- we have reported 92 percent success with this type of treatment in a variety of blood cancers: lymphoma, leukemia, very aggressive types of cancers that everything else failed to treat. Why the others did not respond, we don't know yet. Eventually, we will learn why. But for now, there's not enough experience to answer that question.

OR: Can you explain CAR (chimeric antigen receptor) treatment for blood cancers versus TCR (T-cell receptor) treatment.

Belldegrun: Yes. The investor world somehow decided that CAR's are for treating blood cancers and TCR's are for solid cancers, but that is not the case. This is just the beginning. With CAR, we went after a target, the most low-hanging fruit in the body. Every B-cell – not T-cell – every B-cell in the body has an antigen called CD19. And therefore, when you develop leukemia or lymphoma, there's a proliferation of these B-cells. And there is more of the CD19. So we said, "If we make our target for destruction CD19, we will tell the body, engineer it. You engineer the T-cells to kill every CD19, you will eliminate all the blood disorders." Eventually, CAR will work for solid and for hematologic or for blood disorders, and TCR's which are now believed to work more in the first steps in solid oncology will work also vice versa. We were the first company in the world to do this five years ago. Today, you have Juno, you have Novartis, you have Celgene. You have all the big pharmas getting into it. It's a relatively young field, and CAR and TCR's are two-platform technologies which are very powerful. One is the engineered CAR and the other one is the engineered TCR.

The difference between the two is that CAR is attacking targets that are sitting outside the cell, on the surface of the cell. The immune system can see these targets. The problem is that from all the targets that are known, only five to 10 percent are sitting on the cells. All the rest of the targets are inside the cells, and the immune system cannot see the targets inside the cancer cell. So you needed a technique by which you bring outside the targets from inside the cell.

That's TCR in very simple words. TCR is a technology which brings the target that is buried inside the cancer cell and exposes it outside the cell, so that the immune system can destroy that cancer cell. Kite Pharma is the only company that is currently treating patients with both platforms.

OR: Some of the more recent trials are using combination therapy.

Belldegrun: Not yet. In immunotherapy, yes, but not in engineered immunotherapy.

OR: If it's truly engineered, do you think you'll even need combination therapy?

Belldegrun: A very good point. I don't know, but I believe that in the beginning, everybody goes with a single agent. But since you would not get a 100 percent success rate, the question comes: should we combine it with another type of immunotherapy? I believe that you will see also combination therapies as well, number one. Number two: what are the checkpoint inhibitors doing? The checkpoint inhibitors, which are currently on the market, are anti-PD-1 or anti-CTLA-4. What they are doing is removing the foot from the brake of the immune system. That's all it's doing. It's not pushing on the gas. We, to continue the metaphor, are pushing on the gas.

But the immune system is not meant to be supercharged. So immediately, the body develops a mechanism of down-regulating, downplaying this pushing on the gas, and it's pushing on its own brake. So the other medication, i.e. the checkpoint inhibitors, are removing the foot from the brake. Not letting the body push on the brake.

If you want to win the race, you both push on the gas and remove your foot from the brake. It's very simplistically put, but that's what the logic is. You cannot push very hard on one area without the body saying, "Hey, let's stop and re-evaluate." When we are supercharging it, there will be some mechanism that the body will inhibit it. The Yin and the Yang.

OR: You're saying you're going to need both of them.

Belldegrun: I'm not. No. Right now, we all have outstanding data with single agent treatments, but I think eventually, it might be that for some type of tumors, it will be even better to use a combination. But we don't know. Nobody has done yet a combination immunotherapy with these two types of treatment.

OR: You're two years away from being on the market. That's pretty fast, isn't it, for an oncology product?

Belldegrun: Correct.