Stem Cell Clinic

Cells change type to help or hinder immunity – Medical Xpress

June 5, 2017 The conversion of immune-suppressing cells to immune-boosting cells is beneficial for providing immunity against intestinal worms (H. Polygyrus pictured above), but can make allergies worse. Credit: Mark Wilson. Francis Crick Institute

In news that may bring hope to asthma sufferers, scientists discover a mechanism that provides a possible new target for allergy treatments.

By observing the allergic response in mice with asthma, scientists at the Francis Crick Institute found that white blood cells that normally reduce the symptoms of asthma convert into cells that make allergies worse. The research was funded by the Medical Research Council and the Francis Crick Institute.

"If we can work out what makes the cells change, and how to stop them changing, we might be able to find new ways of tackling allergic responses that make conditions such as asthma worse," says Mark Wilson, Group Leader at the Francis Crick Institute, who led the research.

The findings, published in the Journal of Experimental Medicine, also reveal that this cell-changing mechanism could boost immunity to worms in the intestine, which affect nearly half of the world's population, providing a new approach for vaccines.

"The conversion of immune-suppressing cells to immune-boosting cells is beneficial for providing immunity against intestinal worms, but can make allergies worse," explains Victoria Pelly, first author of the paper, and researcher at the Francis Crick Institute. "If we can find a way to target this mechanism, it will be extremely useful in the clinic."

After infecting mice with intestinal worms, the team took their white blood cells and injected them into non-infected mice, as a sort of 'vaccine', before infecting these mice with intestinal worms. Using a combination of genetic and imaging tools, the team monitored the white blood cells and found that a large proportion of immune-suppressing cells turned into immune-boosting cells to help fight the infection.

To investigate whether the same cell conversion happened in conditions beside worm infection, the team observed what happened to immune-suppressing cells in the lungs of mice with asthma. They found that up to 60% of these cells converted to immune-boosting cells, worsening the symptoms of asthma.

"Even though we notice the same cell conversion in worm infection and asthma, we think that the molecular mechanisms underlying this process are different," says Mark.

The paper,'Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths', is published inThe Journal of Experimental Medicine.

Explore further: Gene therapy could 'turn off' severe allergies

More information: Victoria S. Pelly et al, Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths, The Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20161104

In news that may bring hope to asthma sufferers, scientists discover a mechanism that provides a possible new target for allergy treatments.

(HealthDay)Administration of allergen immunotherapy (AIT) in patients with allergic asthma leads to lower short-term symptom and medication scores, according to a review published online May 19 in Allergy.

Malaria caused by Plasmodium parasites is a life-threatening infectious disease that kills at least half a million people annually while causing over 200 million new infections. In some cases, complications can quickly develop ...

Virtually the entire population of sub-Saharan Africa, and some 70% of African Americans, carry a gene variant (allele) which results in a trait referred to as Duffy-negative. It has long been known that carriers of this ...

Immunotherapy drugs to combat cancer have stimulated tremendous excitement among patients and physicians alike. They debuted in 2011, when the U.S. Food and Drug Administration approved ipilimumab (Yervoy) to treat metastatic ...

Surviving the treacherous journey through the human body from the mouth to the colon takes a special kind of bacterial pathogen. Shigella - a group of bacteria responsible for much of the diarrheal disease affecting children ...

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Cells change type to help or hinder immunity - Medical Xpress

Gene-Targeted Drugs Fight Advanced Lung Cancers – Montana Standard

MONDAY, June 5, 2017 (HealthDay News) -- Two drugs that target genetic flaws are giving people with specific types of advanced lung cancer a chance to live longer and better, a pair of new clinical trials finds.

A newly approved drug called alectinib (Alecensa) works twice as long as the current standard medication in halting cancer growth in patients with ALK-positive non-small cell lung cancer, results from a new global clinical trial show.

ALK is a gene that produces a protein that helps cancer cells grow and spread, according to the American Cancer Society (ACS).

In another study, an experimental drug called dacomitinib delayed cancer growth by about half in non-small cell lung cancer patients who had a mutation of the epidermal growth factor receptor (EGFR) that caused cancer cells to grow faster, a second trial reported. Non-small cell lung cancers comprise most lung cancer cases.

EGFR is a substance normally found on cells that helps them grow and divide, the ACS says.

The drugs, alectinib in particular, will let people live months or years longer just by taking a daily pill, said Dr. Bruce Johnson, chief clinical research officer at Dana-Farber Cancer Institute in Boston. Johnson is also incoming president of the American Society of Clinical Oncology (ASCO).

Alectinib works more than a year longer than crizotinib (Xalkori), which itself supplanted chemotherapy a few years back because it proved more effective with fewer side effects, Johnson said.

"This is kind of a game changer, because the drug itself works at least for two years, plus there are other treatments" that can be substituted when it ultimately becomes ineffective, Johnson said of alectinib. "We used to have to tell these patients 10 or 15 years ago that you've got eight months to a year. Now they most likely have years."

Both of these genetically driven forms of lung cancer are more common in nonsmokers, the ACS says.

The studies were both funded by the drug manufacturers. Hoffmann-La Roche funded the alectinib study. Pfizer and SFJ Pharmaceuticals Group funded the dacomitinib study.

The first clinical trial revealed that alectinib halts lung cancer growth for about 26 months on average. That compared to about 10 months on average for crizotinib, the drug now used as front-line treatment for ALK-positive patients.

Alectinib also works 84 percent better than crizotinib at preventing spread of advanced lung cancer to the brain, because it is better able to penetrate into the brain and kill cancer cells there, said lead researcher Dr. Alice Shaw, director of thoracic oncology at Massachusetts General Hospital Cancer Center in Boston.

About 5 percent of non-small cell lung cancer cases are ALK-positive. That means they have a genetically abnormal protein that fuels cancer growth. In the United States, about 12,500 people are diagnosed with ALK-positive non-small cell lung cancer each year, researchers said in background information.

Alectinib already is approved in the United States as a treatment for ALK-positive patients who no longer respond to crizotinib, Shaw said.

The results should "establish alectinib as the new standard of care" for ALK-positive lung cancer patients, rather than crizotinib, Shaw said.

ASCO expert Dr. John Heymach agreed, calling the clinical trial a "watershed moment."

Not only did the drug work better and longer, but it also produced fewer side effects in patients, noted Heymach, chair of thoracic/head and neck oncology for the University of Texas MD Anderson Cancer Center in Houston.

The most common side effects for alectinib were fatigue, constipation, muscle aches and swelling, while crizotinib patients most often suffered from gastrointestinal problems and liver enzyme abnormalities, according to the researchers.

The second clinical trial compared a new drug, dacomitinib, to the current standard targeted drug gefitinib (Iressa) in treating EGFR-positive lung cancer.

Each year about 15,000 people in the United States are diagnosed with EGFR-positive lung cancer, which involve mutations that increase the growth of cancer cells, researchers said in background notes.

Dacomitinib blocked EGFR mutations more effectively than first-generation drug gefitinib, providing a 41 percent lower chance of cancer progression or death, researchers found. On average, dacomitinib halted cancer growth for 14.7 months in patients, compared with 9.2 months with gefitinib.

"From the perspective of doctors who treat lung cancer daily, this is really a substantial advance," Heymach said, noting that the results put the drug "at the front of the pack in terms of efficacy."

However, dacomitinib also created more side effects, including acne in about 14 percent of patients and diarrhea in 8 percent of patients. Doctors wound up reducing the dosage in about 66 percent of patients as a result of side effects, said lead researcher Dr. Tony Mok, chair of clinical oncology at the Chinese University of Hong Kong.

Heymach said the side effects are "not life-threatening toxicities."

"These are toxicities that doctors who treat this for a living become accustomed to managing," Heymach said.

"At the end of the day, I think we now have one additional choice" in treating EGRF-positive non-small cell lung cancer, Mok concluded, adding that dacomitinib should be considered as a new first-line alternative treatment. The drug has not received FDA approval.

Neither of the tested drugs will be cheap. "Almost all these targeted drugs are thousands of dollars per month," Johnson said.

The results of both trials were scheduled to be presented Monday at ASCO's annual meeting, in Chicago. The findings were also being published June 6 in the New England Journal of Medicine.

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Gene-Targeted Drugs Fight Advanced Lung Cancers - Montana Standard

Column: Stem Cell Therapy A medical revolution – Current in Fishers

Commentary by Dmitry M. Arbuck, MD, President and Medical Director, Indiana Polyclinic

We are at a truly revolutionary time in health and medicine. The introduction of stem cell technology represents innovation on the same level as the development of antibiotics or the invention of modern imaging (MRIs, etc.). Stem cells are already changing the way medicine is delivered, increasing lifespans and saving countless lives.

Arbuck

Scientists and researchers have been studying the benefits of stem cells for more than 30 years. They have found that these special cells provide great benefits all over the body, from muscles and joints to chronic diseases, to growing new teeth. You may have read about athletes treated with stem cells to speed healing after an injury or about burn victims who use stem cell therapy to minimize scarring.

Stem cells used to be associated with embryos, but this is no longer the case. Today, live cells for treatment are either adult stem cells or umbilical cord blood stem cells. Adult stem cells are most likely extracted from tissue, like bone marrow or fat, which can be a painful and invasive process. Additionally, as we age, so do our stem cells, which become less potent and productive over time. Like every other tissue in our bodies, they are exposed to the toxins, radiation and other pollutants in the environment. Umbilical cord blood stem cells are collected from the donated cord blood and placenta of healthy newborns. The cells are then screened for disease and genetic problems. These umbilical stem cells are vibrant, vital and healthy.

When umbilical cord stem cells are infused, they carry a whole host of immune stabilizing factors throughout the body and work to repair the immune system. This is likely why stem cells are so helpful in the treatment of autoimmune diseases such as rheumatoid arthritis, Crohns disease, dermatitis and myasthenia gravis. Other things that may be successfully treated with this therapy include MS, lupus, graft vs. host disease and other immune conditions.

The future is today. For more, visit StemCellsIndy.com.

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Column: Stem Cell Therapy A medical revolution - Current in Fishers

CAR-T Cancer Approach Has Surprising Success in Multiple Myeloma – NBCNews.com

T lymphocyte cells (blue) attached to cancer cells. Steve Gschmeissner / Science Photo Library/Getty Images

Experts at an American Society of Clinical Oncology conference in Chicago, where the results were announced Monday, say it's a first for multiple myeloma and rare for any cancer treatment to have such success.

Chemotherapy helps 10 to 30 percent of patients; immune system drugs, 35 to 40 percent at best, and some gene-targeting drugs, 70 to 80 percent, "but you don't get to 100," said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.

"These are impressive results" but time will tell if they last, he said.

Multiple myeloma affects plasma cells, which make antibodies to fight infection.

More than 30,000 cases occur each year in the United States, and more than 115,000 worldwide. It's the second fastest growing cancer for men and the third for women, rising 2 to 3 percent per year, according to the National Cancer Institute. About 60,000 to 70,000 Americans have it now.

Nine new drugs have been approved for it since 2000 but they're not cures; only about half of U.S. patients live five years after diagnosis.

With cell therapy, "I can't say we may get a cure but at least we bring hope of that possibility," said Dr. Frank Fan. He is chief scientific officer of Nanjing Legend Biotech, a Chinese company that tested the treatment with doctors at Xi'an Jiaotong University.

The treatment, called

Related:

Doctors call it a "living drug"-- a one-time treatment to permanently alter cells that multiply in the body into an army to fight cancer. It's shown promise against some leukemias and lymphomas, but this is a new type being tried for multiple myeloma, in patients whose cancer worsened despite many other treatments.

In the Chinese study, 19 of 35 patients are long enough past treatment to judge whether they are in complete remission, and 14 are. The other five had at least a partial remission, with their cancer greatly diminished. Some are more than a year past treatment with no sign of disease.

Most patients had a group of side effects common with this treatment, including fever, low blood pressure and trouble breathing. Only two cases were severe and all were treatable and temporary, doctors said.

The second study was done in the U.S. by Bluebird Bio and Celgene, using a cell treatment developed by the National Cancer Institute. It tested four different dose levels of cells in a total of 21 patients. Eighteen are long enough from treatment to judge effectiveness, and all 15 who got an adequate amount of cells had a response. Four have reached full remission so far, and some are more than a year past treatment.

The results are "very remarkable" not just for how many responded but how well, said Dr. Kenneth Anderson of Dana-Farber Cancer Institute in Boston.

"We need to be looking for how long these cells persist" and keep the cancer under control, he said.

Dr. Carl June, a University of Pennsylvania researcher who received the conference's top science award for his early work on CAR-T therapy, said "it's very rare" to see everyone respond to a treatment. His lab also had this happen -- all 22 children testing a new version of CAR-T for leukemia responded, his colleagues reported at the conference.

"The first patients we treated in 2010 haven't relapsed," June said.

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Dr. Michael Sabel of the University of Michigan called the treatment "revolutionary."

"This is really the epitome of personalized medicine," extending immune therapy to more types of patients, he said.

Legend Biotech plans to continue the study in up to 100 people in China and plans a study in the U.S. early next year. The treatment is expected to cost $200,000 to $300,000, and "who's going to pay for that is a big issue," Fan said.

"The manufacturing process is very expensive and you can't scale up. It's individualized. You cannot make a batch" as is done with a drug, he said.

Nick Leschly, Bluebird's chief executive, said the next phase of his company's study will test what seems the ideal dose in 20 more people.

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CAR-T Cancer Approach Has Surprising Success in Multiple Myeloma - NBCNews.com