In a breakthrough for leukemia patients that was 20 years in the making, researchers in Pennsylvania say they have developed a groundbreaking technique to create co-called ‘serial killer' T cells that eradicate tumours in patients who have few treatment options left.

Researchers in Pennsylvania say the new treatment involves removing the patient's own T cells, genetically modifying them and then injecting them back into the patient's body, where they seek and destroy cancer cells.

The treatment was tested on three patients with advanced chronic lymphocytic leukemia (CLL). Doctors had little to offer these patients in terms of treatment besides a bone marrow transplant, a risky procedure with a 20 per cent mortality rate that offers a 50 per cent cure rate at best. The new gene therapy treatment led to periods of remission for all patients that lasted as long as a year.

The findings are so significant that they are being published simultaneously in two journals: the New England Journal of Medicine and Science Translational Medicine.

"Within three weeks, the tumours had been blown away, in a way that was much more violent than we ever expected," senior study author Carl June, director of translational research and a professor of pathology and laboratory medicine in the Abramson Cancer Center, said in a statement. "It worked much better than we thought it would."

It appears that funding issues limited the number of participants in this study to three, with the National Cancer Institute and other agencies declining to support the research. A grant from the Alliance for Cancer Gene Therapy allowed the small trial to go ahead.

The first step in the process involves removing the patients' T cells, a type of immune cell, and then genetically modifying them with an antibody-like protein called a chimeric antigen receptor (CAR). The CAR is designed to bind to a protein called CD19, which is produced by chronic lymphocytic leukemia cells. The T cells attack all cells that produce CD19 but ignore other cells, which limits the side effects common with other treatments.

The CAR also contains a so-called signalling molecule that triggers other T cells to multiply, thereby creating more immune cells to attack and kill the cancer cells.

"We saw at least a 1000-fold increase in the number of modified T cells in each of the patients. Drugs don't do that," June said. "In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell led to the killing of thousands of tumour cells -- and overall, destroyed at least two pounds of tumor in each patient."

In the paper published in the New England Journal of Medicine, researchers describe the case of a 64-year-old patient whose blood and marrow were full of tumour cells. On the 14th day after treatment, he began suffering from chills, nausea and fever. Tests showed a massive spike in T cells in his blood that had led to tumour lysis syndrome, which occurs when a large number of cancer cells die off at once. By the 28th day post-treatment, the patient had recovered from the syndrome and his blood and marrow showed no evidence of leukemia.

Dr. Matthew Cheung, an oncologist at Toronto's Sunnybrook Health Sciences Centre and the co-chair of the hematology disease site group at Cancer Care Ontario, called the study "an important advance in cancer therapy." According to Cheung, it proves scientists can safely genetically modify and enhance a patient's immune system to identify and attack cancer cells.

"This is a major step towards individualizing cancer care for patients. These researchers are tailoring a patient's own immune system to attack their cancer cells," Cheung told CTV News.

"Moreover, this approach may target tumour cells in a safer way compared to conventional cancer therapy. Unlike conventional chemotherapy, that non-specifically attacks rapidly dividing cells, this new method is specific in its recognition and destruction of cancer cells alone."

According to the researchers, the treatment essentially reawakens T cells that have been suppressed by the leukemia. It also stimulates the production of so-called "memory" T cells, which researchers hope will protect against disease recurrence.

While the three patients studied experienced remission periods of up to a year, the long-term effects of the treatment are not yet known.

Going forward, according to Cheung, further clinical trials are needed to see if the results can be replicated in a larger population of patients.

"With relatively few patients treated to date, we will have to await larger studies and longer follow-up of treated individuals to be sure these therapies are safe and effective," he said.

Dr. Cynthia Toze of the BC Cancer Agency pointed out that there are a number of concerns with the study, particularly the potential for unexpected future complications.

"Any time someone is suppressing the patient's cells and the patient's immune system, they may be at higher risk for different infections or other potential malignancies down the road," Toze told CTV News.

Toze called the findings "very exciting" but cautioned that it is too early to declare the treatment a cure.

Meanwhile, the researchers plan to test the same treatment in patients with non-Hodgkin's lymphoma and acute lymphocytic leukemia, as well as in children whose leukemia has not responded to conventional treatment.

The researchers also say the treatment sets out a roadmap for treating other cancers, including lung and ovarian cancer, melanoma and myeloma.

With a report from CTV's medical specialist Avis Favaro and producer Elizabeth St. Philip