Aging But Still Protected

June 14, 2013 by

June 14, 2013

By Medical Discovery News

The people who are at the highest risk of dying from common infections like pneumonia, influenza, and colds are 50 and older. Traditionally, scientists believed that as we age, our immune systems weaken, leaving us more vulnerable than ever to infections. But new research suggests that this isn’t completely true – certain parts of the immune system remain fully functional and robust longer.

It is true that older people make fewer antibodies, proteins that attach to viruses and cells infected with viruses to mark them for elimination by the immune system. This explains why some vaccines aren’t as effective in the elderly. The flu vaccine, for example, contains a “dead” virus that stimulates the body to make more protective antibodies against the flu.

However, other vaccines are well-received in older people, like the varicella zoster virus vaccine that prevents shingles. This vaccine does not involve antibodies, but T-cells, which kill infected cells, and memory T-cells, which recognize and respond to a reinfection.

White blood cells, formally called leukocytes, represent an army ready to defend the body from bacterial or viral attacks. T-cells are one type of soldier in this army, responsible for cellular immunity – killing infected cells to protect the body. The thymus, located between the breast bone and heart, produces T-cells. But as people age, the thymus does too.

The thymus shrinks by about 3 percent a year during middle age, and there is a corresponding fall in the production of T-cells. As humans age, their T-cells increasingly become memory cells. Therefore, it’s been assumed that the T-cell response to kill cells infected with a virus is impaired in older adults, making them more susceptible to viral infections.

To test that assumption, researchers at the McMaster Immunology Research Centre in Ontario isolated blood from people with one of three types of viral infections: West Nile Virus, Epstein-Barr Virus, and Cytomegalovirus. They divided the patients into three groups: those under 40, those middle-aged (41 – 59), and those over 60. They then measured the amount, type, and activity of the T-cells in each group. The older group did indeed have a shift toward the production of memory T-cells. But surprisingly, the amount of virus-specific T-cells did not decrease with age – the older group had roughly the same amount as the middle and younger groups.

These results suggest that the thymus continues to play an important role in producing T-cells that target viral infections as we age. It also indicates that vaccines designed to stimulate cellular immunity, instead of antibodies, would be more effective in older people. So the flu vaccine might prevent more flu cases in older people if the dead virus was replaced with a live but weakened virus, but currently that’s not approved in the U.S. for people over 50.

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Bringing HIV Out of Hiding

March 15, 2013 by

March 15, 2013

By Medical Discovery News

Still tall, strong, and vibrant, Magic Johnson radiates the good health he exuded while playing professional basketball more than two decades ago. Yet for all that time he has been living with HIV, an infection controlled with a mix of potent drugs.

Though these antiretroviral drugs are highly effective, finding a cure for the lifelong disease remains elusive mainly due to a hidden pool of HIV-infected cells unreachable by current therapies. Recently a group of scientists successfully activated these cells, raising the hope of finding a cure for AIDS.

When HIV, the virus that causes AIDS, infects a cell, a copy of its genetic information is inserted in the cell’s genome and becomes a permanent part of that cell’s genetic information. After that, all future generations of the cell also contain the virus. 

In particular, HIV infects CD4+T white blood cells that become activated during infections.  After a patient is treated, the HIV-infected cells that survive revert back to a resting state, allowing the virus to become latent, lying dormant and unreachable by the immune system and current HIV drugs. This latent reservoir of infected cells is a major barrier to curing the disease, because anytime they’re activated the once-dormant viruses trigger a new round of infection.

The current standard therapy for HIV is called HAART, Highly Active Antiretroviral Therapy, which consists of three anti-HIV drugs given in combination.  Though highly effective in controlling HIV replication and in prolonged suppression of HIV levels in the blood, HAART isn’t capable of killing the virus in dormant infected CD4+T cells.

In the new study led by David Margolis at the University of North Carolina at Chapel Hill, a drug called Zolinza (Vorinostat) activated the virus in dormant infected T-cells, which may allow the immune system to locate and target the cells for eradication. Recent studies by Margolis and others have also shown that the drug attacks enzymes that keep HIV hiding in certain CD4+T cells.  Zolinza is a histone deacetylase (HDAC) inhibitor that is normally prescribed for mood disorders, certain lymphomas, and epileptic seizures.

Margolis’ team administered the drug to six HIV-infected men on HAART therapy. Within eight hours of taking Zolinza, all patients showed a five-fold increase in the amount of viral RNA, a marker of HIV replication in the CD4+T-cells. This means the latent HIV was activated, which will hopefully make it vulnerable to current treatment, but will more likely pave the way to a means of marking the infected cells for eradication by drugs or the body’s immune system.

The study also showed that while Zolinza promoted HIV replication, the viral loads in the blood did not go up since all the study patients were on the HAART regimen. Scientists will no doubt need to develop several treatment approaches to target latent HIV, but at least this latest discovery offers new hope for a cure.

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Armed Against Cancer

March 11, 2012 by

By Medical Discovery News

March 3, 2012

Armed Against Cancer

Imagine if a patient’s own cells could fight cancer rather than struggle through chemotherapy and radiation. For two decades scientists have attempted to do that with T-cells, but no one came close until the remarkable success of a pilot study at the University of Pennsylvania.

Two out of the three leukemia patients they treated remained cancer free a year after nearly dying. And the third is in partial remission.

The researchers, led by Dr. Carl June, were able to accomplish three things that hadn’t been done together before: engineer T-cells to fight and kill leukemia cells, have them multiply when inside the body, and then diminish and leave a set of memory T-cells to multiply again and kill leukemia cells if they show up later.

The results stunned even the researchers involved, whose intentions were only to test the therapy’s safety. First, they extracted T-cells, a type of immune cell, from the patient and supplied them with a gene that creates something called a chimeric antigen receptor, or CAR, on the surface of T-cells. This new receptor, CAR, is supposed to recognize and kill B-lymphocytes, which grow out of control in a chronic form of adult leukemia.

But in past clinical trials, when these CAR T-cells were transfused in the patient, they failed and died without doing much damage to tumor cells. In this newest study, however, researchers added an extra gene to the T cells called 4-1BB.

The 4-1BB encoded protein enhances the cell’s tumor-killing ability, and instructs CAR T-cells to multiply and persist as memory cells. But its response isn’t so severe that it kills the patient, which has happened in other CAR T-cell trials.

The fascinating part of this study is researchers used a disarmed HIV, the virus that causes AIDS, to deliver these cancer-fighting genes into the patient’s T-cells. Even though the thought of injecting HIV may be unsettling to most people, this disarmed virus isn’t harmful and does not multiply in the body. The choice makes sense because HIV naturally targets and penetrates T-cells.

A few weeks after transfusing these engineered T-cells in patients, doctors could find no cancer cells anywhere. The researchers estimate more than two pounds of leukemic cells were destroyed. As for the third patient, researchers think it’s possible his steroid treatments may explain why he ended up in partial remission.

June’s team is now planning wider clinical trials to include more patients. The aim will be to test the efficacy of the therapy and its adverse effects. For example, one of the targets on the tumor cell is also found on healthy membranes that line the chest and abdomen.

Researchers are optimistic that this therapy can treat not only leukemia, but other serious cancers such as those of the ovaries, pancreas and mesothelioma, a cancer of the tissue that lines most major organs. Scientists believe this study marks a turning point in gene therapy against cancer, and future studies will use its novel approaches to develop life-saving treatments.

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