NEW HAVEN >> Young patients with a particular type of leukemia who have relapsed after going into remission may find new hope through a treatment that involves modifying a patients own T cells, an important part of the immune system, to destroy cancer cells.

While the therapy, in which genes are inserted into a patients T cells, is expected to receive Food and Drug Administration approval soon for pediatric patients, researchers hope that it will be effective for adult patients as well and for more types of cancers, according to Dr. Steven Gore, director of hematologic malignancies at the Yale Cancer Center.

The cancer thats the focus of this T cell therapy is B-lineage acute lymphoblastic leukemia, which is the most common leukemia in kids and its commonly cured in the 2- to 10-year-old age group, Gore said. He said about 70 percent of children with the cancer are cured.

However, the rest suffer a recurrence of the disease even after treatment with chemotherapy and stem cell transplants.

Its getting to be a difficult situation, Gore said.

There are 3,100 cases of children with B-lineage ALL each year, he said.

B cells, also known as B lymphocytes, are white blood cells that produce antibodies, which fight infection. A characteristic of B cells is that they have a protein on their surface called CD19, which is the key to the new treatment.

The new process, marketed by Novartis and first developed at the University of Pennsylvania, involves harvesting T cells from the patient. Novartis then introduces DNA into these T cells, introducing new genes into the T cells, [which] include a receptor that will recognize CD19, Gore said. The genes that are fused into the T cells are manufactured in the lab but are copies of normal human genes, Gore said. The new cell is called a chimeric antigen receptor T cell, or CAR-T cell.

Normal T cells fight disease, and we know that T cells can attack cancer cells as well, but getting them to do so in the host where the cancer has developed is tricky, Gore said. Cancer cells are very similar [to] normal cells from which they derive.

Turning the T cells into CAR-T cells helps by targeting the CD19 marker on the B cells. CD19 happens to be a pretty good target for cancer technology because its only on B cells, Gore said. These new CAR-T cells latch onto the leukemia cells.

Reproducing cells

Then, once they see that theyre needed, the CAR-T cells are going to make more of themselves. Theyre going to make a whole army-full beside what we gave the patient, Gore said. Other genes in the introduced DNA give the immune system the go-ahead to kill these leukemia cells.

The CAR-T cells target both healthy and malignant B cells, but people live all the time without B cells, Gore said, by relying on drugs such as rituximab.

The treatment is not easy on the patient, however. When this massive influx of these new T cells attack all these leukemia cells, youre basically setting up a jihad in your body, Gore said. People can get very critically ill after this therapy, even needing to be treated in the intensive care unit.

Despite the hardship, the FDAs Oncologic Drugs Advisory Committee voted 10-0 on July 12 to recommend approval of CAR-T therapy, and it is very rare that an ODAC approval does not end up in an FDA approval, Gore said.

In one trial, 41 of 50 patients with relapsed or refractory B-lineage ALL each achieved complete remission after three months, Gore said, and 60 percent of those patients were still in remission six months later.

It will be rapidly opened up to adults as well, theres no question about it, he said. Some people think this therapy may replace stem cell therapy and doctors hope it can be given before a patient relapses, avoiding stem cell transplants.

We dont have long-term follow-up to know if these patients are cured, Gore said. Theyve certainly been rescued from otherwise-certain death.

Gore said the Yale School of Medicine has been approached by Novartis to be one of the rollout sites for this therapy.

While the new treatment targets a relatively rare cancer, its likely to be effective in other cancers involving B cells, including other types of leukemia and lymphoma, Gore said. (Not all lymphomas and leukemias are B cell cancers, however.) This rare leukemia has been the subject of all this investigation because CD19 is such a low-hanging fruit, because we can live without B cells, he said.

But the technology can theoretically be adapted to any kind of tumor, he said. Theoretically, you could make a CAR-T to target any particular kind of cancer provided that that cancer expresses certain proteins that are predominantly limited to the cancer and not important vital organs.

Call Ed Stannard at 203-680-9382.

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Rare leukemia targeted by modifying patients' immune cells - West Hartford News