When chemotherapy proved ineffective for 65-year-old William Ludwig, a retired corrections officer from New Jersey a year ago, he signed up to be the first to receive treatment in a bold experiment at the University of Pennsylvania. By then, his life was draining away, as he put it. He thought he had nothing to lose.

The research team, led by Dr. Carl June, removed a billion of William's T-cells (white blood cells that fight viruses and tumors) and engineered them with new genes that reprogram the cells to attack his cancer. A disabled form of H.I.V. -1, the virus that causes AIDS, was employed to transport cancer-fighting genes into the patient's own T-cells. In essence, the team trained Ludwig's own immune system to kill cancer cells. The process is detailed in The New England Journal of Medicine as well as in Science Translational Medicine.

There were no reactions at first but after 10 days, he shook with chills, his temperature skyrocketed while his blood pressure plummeted--William had so rapidly become ill that the doctors moved him into intensive care, warning him that he might die. Fearing the worst, his family gathered at the hospital.

Fast forward a few weeks later. No fever. No leukemia.

All traces of leukemia vanished. No leukemic cells were to be found in his blood or bone marrow; his CT scan was clean. The doctors calculate that the treatment destroyed up to two pounds of cancer cells. One year later, and William is still in complete remission. Before the treatment, there were days when he could barely get out of bed. Now he revels on the green of gulf and works on his yard.

"I have my life back," says William.

"It's great work," said Dr. Walter J. Urba of the Providence Cancer Center and Earle A. Chiles Research Institute in Portland, Ore. He called the patients' recoveries remarkable, exciting and significant. "I feel very positive about this new technology. Conceptually, it's very, very big."

Though Ludwig's doctors do not claim that he is cured, as it is too soon to tell - the research has far to go and the treatment is still experimental and unavailable outside of clinical studies - the treatment has obviously helped Ludwig tremendously. This may be a turning point in the long struggle to develop effective gene therapies to combat cancer. And not just for leukemia--other cancers may also be vulnerable to this breakthrough approach.

Two other chronic lymphocytic leukemia patients were also treated in the experiment; one had a partial remission--his disease lessened but did not completely go away. Another, like William, experienced complete remission. All three were at an advanced stage of the disease, ran out of chemotherapy options, and were not candidates for bone-marrow transplantation.

Dr. Carl June said the results stunned even him and his colleagues, Dr. David L. Porter, Bruce Levine and Michael Kalos. Of course they had hoped to see some benefit of the experimentation, but had not dreamed of seeing complete, prolonged remissions in the patients. When Mr. Ludwig began running fevers, the doctors did not initially realize that it was a sign that his T-cells were furiously battling with his leukemia.

Dr. Walter J. Urba said he thinks the approach would ultimately be used against other types of cancer along with leukemia and lymphoma though he cautions that "For patients today, we're not there yet." And he added the usual scientific caveat: To be considered valid, the results must be repeated in more patients, and by other research teams.

But what profound hope we have for this to be validated!

When Ludwig entered the trial, Dr. June said that he was "almost dead". The trial was Phase 1, meaning that the main goal was to find out if the treatment was safe, and if so, at what doses. Ludwig thought that if the trial study could give him six months to a year, it would be worth it, but even if it didn't help him personally, he felt that it would still be worth helping the study.

"I feel wonderful," Mr. Ludwig said in an interview. "I walked 18 holes on the golf course this morning."

William Ludwig was tremendously week before the study, suffering repeated bouts of pneumonia and wasting away. Now, he is full of energy. He has gained 40 pounds. He and his wife bought an R.V., in which they travel with their grandson and nephew.

"I feel normal, like I did 10 years before I was diagnosed," Mr. Ludwig said. "This clinical trial saved my life."

Reference:

Grady, Denise. "An Immune System Trained to Kill Cancer." The New York Times | Health. The New York Times Company, 12 Sept. 2011. Web. 14 Sept. 2011.
http://www.nytimes.com/2011/09/13/health/13gene.html?_r=2&pagewanted=1&ref=health&src=me.

Posted by Swervesome at 4:38 PM | Permalink | Comments (4)

A blood-borne immune factor present in elderly mice contributes to signs of mental decline when injected into young mice. By inhibiting this blood-born immune factor, youthfulness is restored in old mice, implying that it may be possible to change some of the symptoms of aging in the brain by altering the levels of immune factors in the blood.

The hippocampus, an important sea-horse shaped component of the brain that plays a role in memory, spatial memory, and navigation, loses function and ceases to produce new neurons as it ages. Though this deterioration can be partially reversed when animals regularly exercise thereby stimulating circulation and releasing chemicals and metabolites into the blood, Tony Wyss-Coray of Stanford University School of Medicine wondered if there was a blood-borne element that might contribute to these changes.

Published in August 31, 2011 in Nature, his study implies that it may be possible to change some of the aging symptoms of the brain by altering the levels of immune factors in the blood.

By stitching the flank of a young mouse to the flank of an old one, Wyss-Coray and colleagues formed a conjoined-twin effect, allowing the blood of both mice to mingle. They found that the young animals showed a decline in neurogenesis while the old ones showed new growth as compared to young and old stitched to partners of similar age.

"There seemed to be rejuvenation in the old brain," said Wyss-Coray.

So the researchers extracted only blood plasma devoid of the cells of old mice and injected into the young mice. They saw a similar decline in neurogenesis. It appeared as though an extracellular blood protein was responsible. These mice were then administered a battery of memory tests and mazes. The mice with old blood plasma did not form as robust memories and did not remember the solution to a maze as well as normal young mice--similar impairments found in old mice.

In order to identify the element in the plasma that caused this effect, comparisons were made on the concentrations of blood proteins in the conjoined animal; of six candidate proteins whose levels that changed after the mice were stitched together, CCL11 or eotaxin, a chemokine, demonstrated the most significant change.

"The factor [CCL11] is a surprising character," said Richard Ransohoff from the Cleveland Clinic Lerner College of Medicine. "It's a chemokine that has zero prior neurobiology," he added. Known only for its role in attracting eosinophils or immune cells that play a major role in allergy and asthma, when the researchers injected this chemokine into young mice, a decrease in new neuron formation was observed. This effect was then reversed with an injection of a CCL11-blocking antibody! Observing too how CCL11 fluctuates with age, Wyss-Coray and researchers saw that its blood-levels elevated in mice and in humans with age.

Wyss-Coray agrees that this study opens a floodgate of new questions. But he's encouraged by the possibilities. For example, "if we could rejuvenate or maintain the brain in general," he said, it might delay some of the detrimental effects that cause dementia or Alzheimer's.

References:

S. A. Villeda et al., "The ageing systemic milieu negatively regulates neurogenesis and cognitive function," Nature, 477:90-96, doi:10.1038/nature10357, 2011.

Posted by Swervesome at 8:04 PM | Permalink | Comments (2)