Penn researchers discover new strategy to battle leukemia

In what may be a significant breakthrough in cancer research, a team of Penn doctors has mutated part of the body’s own defense system to battle cancer cells in patients with the most common form of adult leukemia.

The doctors extracted T-cells (which direct the immune system’s response to malignant cells) from the bodies of patients with chronic lymphoid leukemia, genetically modified them to target B-cells where the cancer lives and then reinserted the modified T-cells back into the patients to destroy cancerous cells.

Of the three patients who participated in the clinical study, two have been in complete remission — meaning cancerous cells have not returned or multiplied — for about a year.

“People have been trying this kind of strategy for a few years now and everybody else has had nothing as close as we [have],” said Michael Kalos, professor of Pathology and Laboratory Medicine, director of the Translational and Correlative Studies Laboratory and one of the co-authors of two papers published last week about the treatment.

“Five elements from this study were unprecedented,” explained Dr. Kalos. “One, we used a much lower number of cells than other [studies]. And, once inside the body, the T-cells grew over a thousand-fold.”

Additionally, the T-cells stayed in the patients’ blood stream for much longer than expected. “Every other study, people have … put in a lot of cells and they very quickly disappeared,” Kalos said. “Ours hung around for up to a year.”

Finally, and perhaps most exciting for the medical community, not only did the T-cells remain, a small number of them seemed to mimic the role of memory T-cells, the cells vaccines cultivate when people get vaccination shots. Memory T-cells bear receptors to foreign substances that the immune system has previously been exposed to so that if the cancer ever returns, as was the case in at least one of the patients before undergoing this treatment, the T-cells will regenerate and keep the cancer cells in check.

“It has been almost a year since I entered the clinical trial. I’m healthy and still in remission.,” wrote one of the three clinical trial patients in a statement. “I am still trying to grasp the enormity of what I am a part of — of what the results will mean to countless others with CLL or other forms of cancer.”

For all the success of this project, funding was initially difficult to acquire.

“These trials are enormously expensive and, in the current government environment, funding is so tight,” said David Porter, Director of Blood and Marrow Transplantation at Penn’s Abramson Cancer Center and a major clinician in the treatment trial.

“We tried to get funding,” Kalos said, “but we got turned down [by pharmaceutical companies] because it was too out of the box.”

Pharmaceutical companies, which normally fund clinical trials like this one, could not initially see the viability of commercializing the genetic modification of cells for individual patients’ use, he said.

The research was supported in part by grants from the National Institutes of Health, the Leukemia and Lymphoma Society and the Alliance for Cancer Gene Therapy.

“This is a new sort of model for medicine. It’s personal medicine,” Kalos said. “You have to take cells from each patient and give his own cell back to him or her. It’s not like in a bottle where you can go to the pharmacy where the same bottle can be used by everybody.”

Both Kalos and Porter noted how important Penn’s state-of-the-art resources and facilities have been in helping the team bring this study from the research laboratories to the patients in clinical trials.

“One of the reasons that this was possible was because of the amazing translational research that Penn has,” Kalos said, referring to the process by which medical discoveries are translated into practical applications for patients.

“In terms of translational medicine and cellular therapy,” Porter said, “we are without a doubt leaders in the country and around the world.”

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