Gene Therapy

Gene Therapy Provides Potential Cure for Leukemia

A clinical research trial on three patients at the University of Pennsylvania has yielded what appears to be one of the greatest advances in cancer research in decades.

In the paper published on September 14, 2011, the Penn researchers said that their treatment caused the most common type of leukemia, chroniclymphocytic leukemia (CLL), to disappear in two of the patients and reduced it by about seventy percent in the third patient.

CLL strikes about 15,000 people in the United States and kills about 4,300 every year.

Even though chemotherapy and radiation can hold off CLL for years, the only cure for this form of leukemia has been a bone marrow transplant which requires a suitable match, works only about half the time, and often carries severe, life-threatening side effects such as pain and infection.

The doctors used gene therapy with a harmless HIV vector, a modified form of the human immunodeficiency virus (HIV), to insert a series of unique genes into the white blood cells, making them able to target and kill the cancer cells.

After growing many of these genetically engineered T-cells, the doctors injected them back into the three patients.

Similar experimental treatments for various types of cancer involving re-injected white blood cells have occurred in the past, but they have only managed to kill a few cancer cells before the T-cells started dying out.

The University of Pennsylvania researchers inserted a gene that caused the white blood cells to multiply by a thousand fold inside the body. Dr. Carl Jung, one of the researchers involved in the Penn experiment, described the resultant white blood cells as having “become ‘serial killers’ relentlessly tracking down and killing the cancer cells in the blood, bone marrow and lymph tissue.”

As the T-cells killed the cancer cells, the patients reported having experienced the fevers, aches, and pains that one would typically expect when the body is fighting off an infection, but beyond that, the side effects have remained minimal.

One year ago, William Ludwig, a retired corrections officer from Bridgeton, NJ, signed up to be the first patient to be treated by this bold experiment after chemotherapy failed to treat his leukemia – leaving him with weeks to live and nothing to lose.

After the doctors removed over a billion of Ludwig’s T-cells, a type of white blood cell that attacks tumors and viruses, they injected him with new genes that would reprogram the cells to attack the cancer. The modified cells were then returned to Ludwig’s bloodstream.

No symptoms of this gene therapy appeared at first, but 10 days later, Ludwig’s body was fighting an internal war. His temperature skyrocketed and his blood pressure dropped. His symptoms were so severe that he was moved to the intensive care unit and was warned by his doctors that he might die.

William Ludwig’s family arrived at the hospital, silently expecting the inevitable.

However, after a few weeks had passed, the leukemia and his fevers had completely disappeared – leaving no trace of cancer cells in his blood or bone marrow. The Penn doctors estimated that the treatment had killed about two pounds of Ludwig’s cancer cells.

After receiving the experimental treatment, William Ludwig faced complete remission of his leukemia and told NBC in tears, “I’m closer to the people I love and I appreciate them more… I’m getting emotional… the grass is greener and flowers smell wonderful.”

The other two patients involved in the clinical experiment chose to remain anonymous. But one, who revealed that he was a scientist, said “I am still trying to grasp the enormity of what I am a part of — and of what the results will mean to countless others with CLL or other forms of cancer. When I was a young scientist, like many I’m sure, I dreamed that I might make a discovery that would make a difference to mankind – I never imagined I would be part of the experiment.”

Shivam Patel, sophomore at the University, feels as if “it may be just be a temporary repair, because the human body has many problems associated with it.”

Alteration of T-cells may even have long term effects. But I still think medicine is improving, and will continue to improve to better society.”

Jonas Colmer, a junior at the University, said “the experiment holds exciting new possibilities for large scale studies. However, the research seems too preliminary for widespread use in clinical practice.”

Both the National Cancer Institute and multiple pharmaceutical companies declined to pay for the clinical research.

Neither applicants nor funders addressed the reasons for their denial. However, many believe that the reasons include general shortage of funds and the experiment being too risky.

The Penn researchers did, however, fund the experiment from the Alliance for Cancer Gene Therapy, a charity founded by Barbara and Edward Netter after their daughter-in-law died of cancer.

This clinical experiment holds the applications to provide millions of people suffering from cancer the ability to taste the hope that they have not seen for far too long.

Gene therapy has yet again served to remind us that we are in the middle of the genetic revolution that is expanding and revolutionizing the world of tomorrow’s medicine.