Tag: melanoma
Cancer Vaccines Enter Clinical Trials

Cancer Vaccines Enter Clinical Trials

By Blythe Bernhard, St. Louis Post-Dispatch (TNS)

ST. LOUIS – Is the best treatment for cancer already inside of us? Research is underway at Washington University to test a new approach to cancer treatment. Beyond traditional therapies like surgery, chemotherapy and radiation, scientists want to know if the human body’s own immune system can attack tumors.

They’re testing personalized vaccines designed to target deadly cancer cells in each patient. A vaccine is any substance that prevents or treats a disease with properties of the disease itself. Scientists know that fighting fire with fire works for many viruses like flu, measles or polio. Now they want to test that theory with cancer, but since every tumor is different, every vaccine will be different.

Advancements in genetic sequencing, or decoding the DNA of cells, have made it easier to figure out what makes tumors unique. Scientists have found potential targets in tumor cells that could cause them to break down. Now they’re passing that knowledge on to doctors to try out in their patients with the most challenging cancers. Clinical trials are now enrolling patients with melanoma, brain cancer and breast cancer.

The concept is hypothetical. The research is experimental. There is no proof that it works.

But after staring down deadly cancers, tumors that have spread, and patients who are out of options, doctors are intrigued.

For decades, scientists have gone back and forth on whether the immune system – the body’s defense mechanism – has anything to do with cancer. In the 1950s a concept called cancer immuno-surveillance took hold, meaning that the immune system could recognize tumor cells as foreign. By the 1970s the theory was rejected after laboratory mice with weak immune systems did no worse than normal mice when they developed cancer.

Most cancer scientists moved on to trying different pharmaceutical routes for new treatments. Robert Schreiber of Washington University wanted to know more about those mice. He started more sophisticated tests with mice that lacked a critical gene that allowed the immune system to make lymphocytes – white blood cells that defend the body against disease.

“What we showed conclusively was mice that had defects in the immune system got tumors more quickly and in higher incidences than normal mice,” Schreiber said.

And with that, the concept of cancer immunology was back. The Center for Human Immunology and Immunotherapy Programs at Washington University launched last year with Schreiber as director to help doctors use the immune system to fight cancer and other diseases.

Other medical centers around the world have taken different approaches to cancer immunology. Duke University is working with a polio virus vaccine to induce the immune system to fight brain tumors. The Mayo Clinic is doing a similar trial with a measles vaccine. Other clinical trials involve reprogramming the immune system’s checkpoints that prevent it from attacking certain cells.

Washington University leads the study of personalized cancer vaccines. With help from their genetic sequencing labs, local scientists try to isolate the best antigen targets – or the most dangerous mutated cells – from each patient’s tumor to vaccinate against.

Vaccines are typically viewed as preventive, such as flu shots to help avoid flu infection. Cancers known to be caused by viruses can also be prevented this way. The HPV (human papillomavirus) vaccine can prevent some cervical cancers and the hepatitis B shot protects against development of liver cancer caused by that virus.

Scientists now think vaccines can also be used to stimulate the immune system to fight cancers that are already formed. But without a known virus or other cause, scientists must figure out what differentiates a patient’s tumor cells from healthy cells. Then they must try to vaccinate against mutations, called neo-antigens that occur only in the bad cells.

The immune system is a finely tuned machine that is difficult to manipulate. One challenge is turning up a patient’s immunity without harming healthy cells, the process that happens in autoimmune disorders like multiple sclerosis. One type of immunotherapy, called checkpoint blockade, is risky because it can backfire and make the patient vulnerable to an overly aggressive or weakened immune response. Cancer vaccines, in theory, could be safer because they activate more highly precise targets.

“The real essence of that vaccine design is picking out the peptides (proteins) that have the strongest interaction with the patient’s immune system,” said Elaine Mardis, director of technology development at the university’s McDonnell Genome Institute. “It’s a different answer for every patient.”

Melanoma
The first human trial to apply this concept included three patients with melanoma whose cancer had spread to their lymph nodes. After surgeries to remove their tumors, their cancerous and healthy cells were sequenced to identify mutations. The patients received an infusion using cells from their own immune systems. The treatments stimulated the immune system through a boost of protective T-cells.

After 20 years of specializing in treating deadly skin cancers, the results published earlier this year were gratifying for Dr. Gerald Linette, a co-leader of the trial. But he urges patience to those looking for quick answers.

“(We) are still really the only lab that’s done this in people, and that’s three patients. I think that we have to be very cautious. Time will tell if this is going to work or not,” Linette said.

His partner in the trial, Beatriz Carreno, said genetic sequencing technology has sped the process of using mutations to encourage the immune system to fight cancer. They are now expanding the clinical trial to include more patients.

Brain cancer
Brain tumors are particularly challenging for immunotherapy targets because the molecules are more diverse compared to other cancers. And the immune system works differently in the brain than it does in the skin or other areas of the body. Messing with the immune system in the nervous system can lead to paralysis or brain damage.

Genetic sequencing creates a search party for “the Achilles heel in each patient’s tumor,” said Dr. Gavin Dunn, a neurosurgeon. A clinical trial is underway to test vaccines against the most deadly brain tumors, called glioblastomas. The first patient will get a personalized vaccine in the next few weeks.

Breast cancer
Dr. William Gillanders led a study in 2010 on a vaccine that used a target called mammaglobin-A, a protein that is expressed in most breast cancers. The vaccine proved to be safe in women who had late-stage breast cancer that had spread to other parts of the body. The women had previously received traditional surgery, chemotherapy and radiation treatments.

Close to half of the 14 patients who received the vaccine had no tumor growth after one year, compared to one-fifth of the 12 patients who did not receive the vaccine.

Michelle Ashby of O’Fallon, Ill., was one of the patients who received the vaccine after she was diagnosed with stage four breast cancer at age 40.

“I knew there needed to be more research on breast cancer and if the study didn’t directly give me benefit, I felt confident it would give benefit to my daughter and other people who are struggling with breast cancer,” Ashby said.

For the next 5 years, Ashby had no cancer recurrence. In August, doctors found some cancerous growth in her breast tissue and it was removed surgically.

“I have statistically beaten the odds of what was expected of my survival,” said Ashby, now 46.

That initial research on the mammaglobin-A vaccine will be expanded with more patients, and new clinical trials are open to test personalized vaccines for breast cancer.

“Now that we understand that there is this very dynamic interaction between the immune system and cancers,” Gillanders said, “a lot of people think that immune responses will be more effective” with personalized vaccines.

Drug companies are not enthusiastic about the idea of personalized medical care that would require a different vaccine for each cancer patient. But new biotech companies are forming to take this approach. Schreiber of Washington University is a co-founder of one of these companies, Boston-based Neon.

Schreiber said that in five years, scientists should have a good idea if cancer vaccine treatments will be ready for general use. A lot of evidence will be required to prove that the immune system can effectively kill off cancer.

Personalized vaccines can’t be mass manufactured for pharmacy shelves. But the process of making them can be streamlined, doctors say. The process that wasn’t even possible five years ago has now been expedited to a few months from genetic sequencing of a patient’s tumor to the injection of the vaccine. The work is a classic example of moving basic science out of the laboratory and into the doctor’s clinic.

The looming question is what happens next. Dunn, the neurosurgeon who specializes in the deadliest type of brain tumors, said he believes in the basic science behind cancer vaccines.

“I really want to be measured about the expectations because we just don’t know yet,” he said. “But I’m an optimist by nature, and I’m extremely hopeful that what we’re learning in cancer immunotherapy will really bring us to a place where we can help patients.”

(c)2015 St. Louis Post-Dispatch. Distributed by Tribune Content Agency, LLC.

Photo: National Cancer Institute via Wikimedia Commons

This Week In Health: Put Down The O.J.

This Week In Health: Put Down The O.J.

“This Week In Health” offers some highlights from the world of health news and wellness tips that you may have missed this week:

  • The California state legislature passed a mandatory vaccine bill that could be a game changer. Unlike other public health legislation mandating the vaccination of children, the new bill, which Governor Jerry Brown signed into law Tuesday, makes no exceptions for religious or “sincerely held” personal beliefs — which is to say, nothing the anti-vaxxers can claim will excuse them from vaccinating their children against whooping cough, measles, and other perfectly preventable illnesses. The bill was introduced after a measles outbreak that began in California earlier this year and was largely attributed to the anti-vaccine movement that has a disturbingly strong hold on certain parts of the state.
  • The Food and Drug Administration (FDA) is cracking down on electronic cigarettes. E-cigs — little suckable pens that vaporize liquid nicotine — have existed in a regulatory limbo since they came into popularity a few years ago. According to the AP, an “uptick in nicotine poisonings reported by emergency rooms and poison centers nationwide, many involving infants and children” has compelled the FDA to consider requiring that vials of liquid nicotine used to refill e-cigs, as well as other non-tobacco nicotine-packed consumables (like lotions, gels, and drinks), use child-resistant packaging and stronger warning language on the labels.
  • Everything is bad for you — including, possibly, citrus fruit. This is according to the results of a study, published in the Journal of Clinical Oncologywhich found a potential link between malignant melanoma and consumption of citrus fruits. This is because fresh citrus fruits contain furocoumarins, photoactive compounds that can heighten an individual’s sensitivity to the sun. “Until we learn more about these furocoumarins,” said the senior author of the report, “those consuming fresh citrus fruits on a regular basis should be extra careful with sun exposure, and depending on their outdoor activities they should wear appropriate sunscreen, hats, and sun-protective clothing.” The report’s authors cautioned that more research was needed and a single study didn’t prove anything. Furthermore, researchers only asked participants about their intake of grapefruits and oranges — so lemons and limes may still be safe.

Photo: Caitlin Regan via Flickr

Melanoma Risk Is Higher For Flight Crews That Work At 40,000 Feet

Melanoma Risk Is Higher For Flight Crews That Work At 40,000 Feet

By Karen Kaplan, Los Angeles Times

Attention pilots and flight attendants: For your safety, please fasten your seat belts, note the location of the aircraft’s emergency exits — and be sure to apply plenty of sunscreen to reduce your risk of melanoma.

When it comes to the risks of flying, skin cancer may not be the first health hazard that comes to mind. But a new study in JAMA Dermatology says that pilots are 2.22 times more likely than folks in the general population at large to be diagnosed with melanoma. For members of the cabin crew, the risk was 2.09 times greater.

Melanoma is the sixth most common cancer in the United States, according to the National Cancer Institute. Although other types of skin cancer are diagnosed more frequently, melanoma is more likely to be fatal, the American Cancer Society says. An estimated 76,100 Americans will be diagnosed with melanoma this year, and about 9,710 will die from it.

Dozens of studies have examined melanoma risk in flight crews, since working at 40,000 feet means greater exposure to cosmic rays and ultraviolet radiation. For the new study, researchers from the University of California, San Francisco combed through data on 266,431 participants in 19 published studies to see whether the danger was real — and if so, how big it was.

They found that for pilots and flight attendants, the risk of developing melanoma was more than double the risk seen in people who worked on the ground. However, only pilots faced an increased risk of death from the cancer — their mortality risk was 83 percent greater than for those in the general population. (For those who worked in the main cabin, the risk of dying from melanoma was actually 10 percent lower.)

The study authors noted that exposure to cosmic radiation is not likely to be a factor for melanoma. Many studies have measured the cosmic radiation that finds its way into a plane, and the amount is “consistently below the allowed dose limit of 20 mSv/y,” or 20 millisieverts per year. (A typical American is exposed to about 3.6 mSv per year, according to this report from the Environmental Protection Agency.)

UVB radiation probably isn’t the culprit either, since fewer than 1 percent of this radiation can penetrate aircraft windshields, the researchers wrote.

UVA, on the other hand, can penetrate glass, and the higher a plane flies, the more intense UVA radiation becomes. When planes fly above clouds or snow-covered mountains, they are exposed to even more UVA reflected from below, the researchers wrote. Studies of cells in lab dishes and in animals show that UVA damages DNA, causing the mutations that can lead to cancer.

It’s possible that when they are on the ground, pilots and flight attendants are bigger fans of activities that would increase their risk of melanoma, such as frequenting tanning salons. So far, there’s no hard data suggesting that this is the case, the UC San Francisco researchers wrote.

Instead, they noted that multiple studies have found that the more hours a member of the flight crew spends in the air, the more likely he or she is to be diagnosed with melanoma.

AFP Photo/Saul Loeb

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Skin Cancer: Not Just A Summer Thing

Skin Cancer: Not Just A Summer Thing

Summer is ending and with it those long, lazy weekend days at the beach or, pool, getting in some extra hours of cycling, running, and walking, or just hanging out on a lawn chair with friends and some cold drinks.  The sun is strong and hot and oh so relaxing. It’s just the thing you need to unwind from the work week. It’s so comforting in fact that most of us forget that in those rays lurks serious danger, even death. Haven’t figured out where we’re going with this yet?  Skin cancer!  And don’t think it’s something you only have to worry about in the summer. The sun is with us 365 days a year, and even though the weather may be cold in your part of the country, wherever the sun shines, skin cancer is a risk.

According to the Skin Cancer Foundation, there are three main types of skin cancer, all with somewhat similar sets of symptoms. And skin cancer, or more accurately cancers, can happen to anyone, at any age, and of any skin color.

Some 2.8 million Americans a year are diagnosed with basal cell carcinoma or BCC, the most common form of skin cancer. So called because it occurs in the basal cells of the skin – the inner part of the skin’s outer layer (epidermis), BCC often looks like a sore that doesn’t heal, a patch of pink or red, or a shiny bump.  Though it rarely spreads beyond the original tumor site, and therefore is rarely life-threatening, BCC can be disfiguring if left untreated. The most frequent cause is the sun’s UV (ultra-violet) radiation, and what you need to know is that you are at risk whether you routinely spend time baking in the sun or you just subject yourself to infrequent intense bursts.

In addition to basal cells, the skin’s epidermis has many layers of squamous cells, and these can be the location of squamous cell carcinoma or SCC.  Like BCC, their initial symptoms can be a sore that doesn’t heal, a patch of pink or red, or a shiny bump, that’s where the similarity ends.

Caused mainly by cumulative, as opposed to short-term exposure to the sun’s UV radiation, if left untreated SCC can be disfiguring and can even kill you if it spreads to other organs (yes the skin is an organ). The Skin Cancer Foundation estimates that 700,000 people are diagnosed with SCC each year, and of those some 2,500 cases result in death. What’s more, although they occur mostly on areas of the body that get frequent sun exposure (arms, legs, face, ears, lips, torso, feet), they can crop up in the mucous membranes and the genitals.

Of the three most common forms of skin cancer melanoma is the most dangerous. Melanoma develops when skin- cell mutations (defects in a cell’s genetic material) are generated by damaged DNA – damage such as that caused by UV radiation from the sun or tanning beds. The result is rapid and uncontrolled growth in the pigment-producing cells (melanocytes) of the epidermis. Melanomas often resemble moles, and some even develop from moles. Their color ranges from black or brown (the majority) to pretty much anything –  skin-colored, pink, red, purple, blue or white. Again, UV radiation is the cause, and those with a family history are at higher risk. Caught and treated early on, it’s usually curable, but note that the US death rate from Melanoma is nearly 10,000 per year.

Obviously the best way to treat skin cancer is to prevent it.  Check out the Skin Cancer Foundation’s Prevention Guide for helpful tips. Your life may depend on it.

Photo: cancer.gov