Regulating Gene Expression Pushes Tumors into Remission


A study published online by the journal Science Translational Medicine discusses a new experimental treatment for a rare, deadly leukemia (blood cancer) that can send the disease into remission even in those patients for whom the standard therapy has failed. Such a treatment can buy patients more time to have a stem cell transplant that could save their lives. This study was only a small pilot study, but these findings are potentially revolutionary.

“It was unbelievable, really, seeing a patient who had already failed Campath [the drug typically used to treat the disease] literally going back into remission,” said Thomas P. Loughran Jr., MD, the director of the University of Virginia Cancer Center, who also served as one of the lead researchers of this study. “We were able to get every single patient back into remission.”

This new approach for battling T-cell prolymphocytic leukemia combines immunotherapy, which boosts the body’s immune system, with the manipulation of gene activity. Such a strategy might cast the mold for treatments for not only T-cell prolymphocytic leukemia, but other cancers as well. “There’s been a revolution in the last few years seeing success with immunotherapy, and people speculated that perhaps if you combined epigenetic and immunotherapy, that might be even more spectacular,” Loughran said. “This is proof of principle that this might be true.”

The pilot study, led by Loughran at UVA and Elliot Epner, MD, at Pennsylvania State University College of Medicine, looked at eight patients with T-cell prolymphocytic leukemia, which is an aggressive cancer that is extremely difficult to treat. T-cell prolymphocytic leukemia is also extremely rare and appears mostly in older men.

Cancer cells in patients with T-cell prolymphocytic leukemia have a cell-surface protein called CD52. By using an antibody to CD52, in the form of a drug called alemtuzumab (a monoclonal antibody to CD52), some patients can be driven into complete remission that lasts, for the most part, between 6-12 months. Alemtuzumab binds to CD52 and directs white blood cells to destroy them (see here).  However, if patients do not receive a bone marrow transplant, the cancer will come back and the cells will not be as sensitive to alemtuzumab. The reason for this resistance is that the cancer cells have down-regulated the expression of CD52. In this reports, patients were given drugs that prevent genes from being silenced (known as histone deacetylase inhibitors). The data from this study shows that the co-administration of epigenetic agents can overcome resistance to alemtuzumab, since the histone deacetylase inhibitors prevented the cancer cells from down-regulating their CD-52 genes.

Alemtuzumab

Although this experimental approach did not cure the patients, it did send them all into remission. Furthermore, it works as well as predicted; patients could be re-treated and receive the same benefit each time. These treatments gave patients vital time as they looked for a suitable bone marrow/stem cell donor. Patients with T-cell prolymphocytic leukemia must have disease that is in remission in order to first receive the transplant.

There are limitations to this approach. Mounting toxicity limits how many times the treatment can be administered. Secondly, the suppression of the immune system can lead to infections and other complications. But the treatment has made a significant difference for all those patients who participated in this study. One patient was expected to live only four months but survived 34. Three others were still alive at the time the researchers were compiling the trial results.

The drugs used in the treatment are already commercially available, meaning doctors could, in theory, administer the treatment without further testing. Loughran, however, believes there needs to be additional study, hopefully in larger trials, but the rarity of the disease makes recruiting subjects difficult. Loughran encourages patients with the disease to consider seeking treatment at UVA. “We’d be very glad to see them here, if they want to come see us,” he said.

Advertisements

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).

One thought on “Regulating Gene Expression Pushes Tumors into Remission”

Comments are closed.