Clinical Trials Lymphoma Use Immunizations Melt Tumors

The preliminary results of three clinical trials, involving 60 patients who had two types of lymphoma, have been encouraging, according to Joshua Brody, M.D., director of the Lymphoma Immunotherapy Program at the Icahn School of Medicine at Mount Sinai in New York.

Brody sat down with Healthline to discuss the new approach he is testing.

In the past few years, research has provided clear evidence that immune-based therapies can cause long-lasting tumor regressions in different types of cancers, according to Brody. He explained that some of these therapies get the patient’s immune system to attack their own cancers. These therapies have been most successful for melanoma, lung cancer, bladder cancer, and kidney cancer. However, these therapies have their drawbacks.

“Those big trials have been with immune therapies called checkpoint blockade antibodies. That approach frees up the whole immune system, and as the dosage of these medicines increase, some patients can get significant autoimmune side effects. The therapies can attack the colon, intestines, and skin, which is an important downside,” said Brody.

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Two Types of Immune Stimulants are Administered

Brody continued, “Our approach is different in that it tries to focus the immune response specifically to the tumor by administering two types of immune stimulants directly into a patient's tumor.”  

Noting that he worked on a “version 1.0” of this approach when he previously worked at Stanford University School of Medicine, Brody said that while the team there had some good responses, overall only a minority of patients responded. In the current work, which he dubbed version 2.0, the focus is on bringing special immune cells, which are called dendritic cells, to the patient’s tumor first.

"The first part of the recipe is using a medicine called Flt3L, to bring the person’s own dendritic cells to the tumor," he explained. "Then we turn on those dendritic cells with a second ingredient called Poly-ICLC, which is a TLR agonist, or TLR activator. TLR is a class of molecules that are on the surface of dendritic cells.”

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Patient’s Immune System Learns and Attacks Tumors

Pointing out that the 2011 Nobel Prize was awarded for the discovery of dendritic cells and TLR activators, Brody said that the scientific community agrees that dendritic cells and TLR activators are important and powerful, but they haven’t been exploited to treat patients with cancer. “That is what we are trying to do. We bring these special immune cells to the tumor with the first type of injection, and then we activate them with the second injection. We let the person’s immune system learn from that and go and attack the tumors everywhere.”

Preliminary results indicate that patients’ tumors are “melting away,” said Brody. He is hopeful the tumors will stay away for a long time and maybe even forever.

Three trials with a total of 60 patients were completed using the version 1.0 approach, which administered only one of the immune stimulants, the TLR activator, directly into patients' tumors. The first two trials treated 15 patients each, and the third trial involved 30 patients. Forty-five patients had B-cell lymphoma, and 15 patients had cutaneous T-cell lymphoma, which is a lymphoma of the skin.

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Low Doses of Radiation Are Administered

After a medicine called Flt3L is given to bring the dendritic cells to the tumor, low dose radiation is given. Radiation therapy is usually given 30 days in a row and it has some side effects, but in this case, Brody said, "a mini baby version of that is given just two days in a row. It’s a small fraction of the amount of radiation, but we think it is still important."

Brody went on to explain that the dendritic cells "come to the tumor and the radiation sort of spills the guts of some of the tumor cells; it kills a few of the tumor cells, and the stuff inside is what the dendritic cells present to the immune system. We call them tumor associated antigens."

He added, "The radiation is good at doing the job of killing a few tumor cells that present to the immune system, but because it’s such a tiny fraction of standard radiation therapy, the radiation is quite benign. It’s given for about two minutes each day, and there are no real side effects from that.”

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Results Are Better than Anticipated

When asked if there had been surprises thus far in the clinical trials, Brody said, “It made good sense that this should be even better than the version we did in California, but that’s no guarantee. I was still delightfully surprised that it worked as well as it did. We thought we would see a little something, but so far we are doing very well. It’s a very preliminary result, but so far it worked better than I would have hoped.”

Among the most impressive responses was a patient with advanced Stage B cell lymphoma who had complete regression of all the tumors visible on CT scans and who has stayed in remission for more than four years so far.  

Noting that a number of different trials using different approaches are underway, Brody said, “This is the most novel. Hopefully we are going to bring this approach to other types of lymphoma and to other types of cancer. That will take a couple of years to do, but hopefully we will do that as soon as possible.”

Will the clinical trial findings become a new standard of treatment? Brody answered, “It has the potential for that, but it is far away. To become a standard therapy, we generally need to treat hundreds of people to prove it is effective and safe. We are nowhere near there yet. We have treated just the first few people. The plan is to treat another 30 patients, and if we prove it is effective, we will take a fresh start and try to treat many more with this kind of lymphoma, and expand it to different types of cancer as well.”

For more information about participating in the clinical trial, contact Julia Howard, clinical research coordinator at Mount Sinai, at julia.howard@mssm.edu.