Serial killers on cancer

Dr. Rosenberg has been operating on patients for years. He deals with cancer, and for one special patient their own immune system took out their cancer cells. Thinking that this person had a special blood type, he transfused it into another patient with cancer. He was however, unsuccessful. He did learn though a new technique on a way to kill cancer. This technique is called "cell therapy." The patients t-cells are extracted from the body and then modified to recognize and destroy cancer. These t-cells are then multiplied millions of times and then put back into the body to fight the cancer. These cells are known as "serial killers" because they can kill thousands of cancer cells. Cell therapy is a unique treatment because it is using a live thing to fight the cancer and it is unique to every person. There have been side effects on a few patients, but research is still going on. These killer cells are mostly used on blood cancers. This article kept my attention the whole time. This could change the whole world, and lead to a cure if further research is as successful as this. Cancer amazes me because it is a mystery and always changing. Today every single person has been effected by some type of cancer, this could lead to solving one of the worlds greatest mysteries. Dr. Rosenberg looked at cancer in a different way and made me think in a different way as well. I would love for him to publish more about this research so I can keep up to date on it. 

Article: https://www.nytimes.com/2016/08/02/health/cancer-cell-therapy-immune-system.html?action=click&contentCollection=health&region=rank&module=package&version=highlights&contentPlacement=1&pgtype=collection&_r=0

Related article: http://annualreviews.org/doi/abs/10.1146/annurev.immunol.25.022106.141527

The link between coeliac disease and wheat

When eating at a restaurant in America, one cannot ignore all the items that contain bread or pasta. Wheat is a crop that has become the soul of Americans; however, it can be toxic to people who suffer from coeliac disease. This is because wheat is a type of grain that contains gluten, which is a mixture of proteins that can be toxic to those individuals. When consumed, patients that have coeliac disease experience an immune response in their bodies to the gluten.

Coeliac disease is common in the US and affects people of all age groups both male and female. It is an autoimmune disease in which the lining of the small intestines becomes inflamed and flatted which leads to bowel damage.

Scientist are on the search for the elements that make gluten toxic. In an article published in the journal "Food Chemistry" scientists wanted to learn about the link between different wheats and their toxicity. They did this by analyzing various kinds of wheat from several countries; specifically epitopes which is a component in wheat that is responsible for the autoimmune response in patients. T-lymphocytes are a type of cell in the immune system that contain an antibody that is capable of recognizing the toxic component in wheat. The scientists look at how the T-cells responded to different wheats to determine its toxicity. Their results revealed that it is difficult to select for a variety of wheat with no toxicity because the genetic diversity is too great. The property of gluten is also related to the strength of the flour and the viscoelasticity of the bread dough. This study is a step towards revealing the potential of production practice for wheat safe for celiacs. It suggests the selective modification of toxic components.

Hopefully, this enables products to be developed that are safe for celiacs. It would improve the nutritional diets and quality of life for those people.

Gene editing saves girl dying from leukaemia in world first

For the first time, gene editing has saved a little girl's life. Layla, a one-year-old girl who was dying from leukemia, was treated with an experimental form of gene therapy using genetically engineered immune cells from a donor after all other conventional treatments had failed. Normally, immune cells from the patient's body are removed, genetically altered to attack the cancerous cells, and placed back into the body. In Layla's case, she did not have enough T-cells (cells that are part of the immune system) left after cancer treatments, so a donor's cells were needed. 

If a donor's T-cells are not perfectly matched, they will recognize all cells of the recipient's body as foreign. To prevent this, the team responsible for the genetic editing disabled the gene in the donor's cells that makes the receptor that allows the T-cells to recognize foreign cells, therefore eliminating this problem. Another issue to overcome is that one of the drugs (an antibody) given to cancer patients to destroy their immune system will also destroy the donor's T-cells. To counter this, the genetics team also disabled another gene in the donor's T-cells, which made them invisible to the antibody drug.

The method used to disable genes can sometimes make cuts in the wrong places, which carries a small risk of causing adverse effects such as turning cells cancerous. However, Layla was given a second bone marrow transplant to restore her own immune system after three months, and these healthy immune cells recognized the donor's cells as foreign and destroyed them. Now, she no longer has any genetically modified cells in her body.

This is an amazing step forward in the fields of genetics as it relates to medicine. Clinical trials are underway in many countries using these methods, and hopefully it will lead to a permanent treatment of many different kinds of cancers.

CRISPR Editing Helps in the Fight Against Cancer

Scientists at the University of California, San Francisco have found a new way of fighting cancer with the use of CRISPR gene editing in T-cells. T-cells are a big part of the immune system and help protect the body from disease. This technique is used to add or delete base pairs at a specific loci. In order to understand the technique, you must first understand what CRISPR is. CRISPR is a naturally occurring part of the immune system in many bacteria. Cas enzymes are used in conjunction with this to cut out specific parts of DNA sequences. The CRISPR DNA sequences tell the Cas enzymes (usually Cas9) where to cut. In this case, a scientist would "feed" the Cas 9 a sequence and the CRISPR would be transported into the cells through a virus.

Alexander Marson and his team have found a way to use this technique to strengthen T-cells against cancer cells. The team used an electrical field to create holes in the cell membranes of the T-cells rather than using a virus. This allowed them to forcibly insert CRISPR into the cells. They were able to alter the DNA down to individual letters rather than large chunks.

When cancer attacks T-cells, they alter a particular gene called PD-1. This tells the T-cells to stop fighting to prevent harm to normal cells, but it's really doing so to stop fighting cancer cells. The research team believes they can use the editing technique to alter the PD-1 gene to get the T-cells to fight back against the cancer cells. The issue with this technique is that there is no telling how long the T-cells will remain in the body and if they begin to attack normal cells it would be a huge issue. This must be addressed before actually being able to use this technique on people.

This technique has been controversial since it was discovered. If improved, it could provide ways of editing genes in any organism. It could provide ways of altering genes in embryos eventually, which could lead to many ethical problems. On the other side, it could help find new therapies for curing the incurable. There is no way of knowing where this technique could take us, but it definitely needs to be researched more to find out.

Is There a Potential Cure for HIV?

It all started with the “Berlin Patient” in 2007. Timothy Brown was cured of HIV when given the stem cells of another patient who was naturally immune to the disease. When this happened two companies, Sangoma and Calimmune, took the opportunity to attempt to recreate the natural immunity to HIV in a lab. This natural immunity occurs because of a gene mutation on the CCR5 gene which is located on CD4 T-cells. When this gene is disable HIV cannot attack the T-cells.

Sangamo was the first to attempt the recreation in 2009. Lead by Carl June from the University of Pennsylvania, a team of researchers and doctors removed CD4 T-cells from patients with HIV. The study then focused on disabling the CCR5 gene alleles and then returning the modified cells to the patient. It was stated that this did no harm to the patients and the altered genes had a half-life of 48 day, which is expected because “…T-cells are not permanent residents of the body”. In fact, several of the patients in this study even exhibited a decline in their HIV levels.

The next company to attempt to recreate the natural immunity to HIV is Calimmune. In 2013 a team led by David Baltimore and Irvin Chen decided to take a different approach to solve the task at hand. Instead of focusing their work on T-cells, they decided to take advantage of blood stem cells. This approach is different because blood stem cells, unlike T-cells, are permanent residents in the body. During this study patients were “given back both their own T cells, and longer-lived HSCs [blood stem cells], both with the CCR5 gene disabled using hairpin RNAs delivered by a lentivirus.” By doing this they hope that these blood stem cells can continue to produce T-cells with disabled CCR5 gene alleles throughout a patient’s lifetime.

Despite the fact that neither of these studies have conclusive clinical trials yet, Harvard University has decided to be next in the search for a cure for HIV. Their approach will include new CRISPR/Cas technology which has already proven effective in mice. It was stated that Harvard may even apply for clinical trial approval in five years.

Article: http://www.biosciencetechnology.com/articles/2014/11/fighting-hiv-stem-cells-and-cutting-edge-genetics

Related Article: http://www.nejm.org/doi/full/10.1056/NEJMoa1300662

New Genetic Clues Found in HIV-1 Immunity.

         For many years, doctors have been perplexed on how some people are ravaged by the HIV-1 virus and others were able to avoid the virus from gaining a foothold in their immunity system. Researchers from the University of Minnesota may have found a weakness in the virus. This could potentially open a door to new treatments. 

         HIV-1 attacks T-cells (lymphocytes) in the immune system. The virus then attaches to the T-cell's molecular machinery destroying the original cells. The person is susceptible to deadly diseases and viruses. The T-cells are not completely alone, they have an anti-virus defense mechanism a protein called APOBEC3s "they have the ability to block the HIV-1s replication." Unfortunately HIV-1 also has a counter protein called Vif that cons the T-cells into destroying the APOBEC3s. 

          A research team decided to build on this original research led by doctoral student Eric Refsland and Reuben Harris of the University's College of Biological Sciences and Medical School. The researchers decided to take a closer look to see if there was a genetic variation in the susceptibility of HIV-1. They found that the "HIV-1 boosts one kind of production of the APOBEC3, the APOBECH." This led the researchers to believe that this was a main player in fighting the virus. The researchers used an experimental separation technique called mutagenesis. The researchers found that "different people have different strengths/potencies of APOBEC3H, with some proteins expressed stably and other inherently unstable." The stable variations were able to limit the success of the replication of the HIV-1 virus if the HIV-1 virus had a weak version of Vif. Unfortunately they were not able to stop the replication if the HIV-1 virus had a strong version of Vif. Refsland and Harris think the next step "is to figure out how to stop Vif from disabling the APOBEC3 enzymes."

       This article shows a potential new pathway that could lead to a cure for HIV-1 in the near future. This could help the millions of people that are currently diagnosed with HIV and family members that are affected. This is very early research, so you just hope that this cure pan outs, unlike so many other HIV-1 'cures' that have come before. 

Original Article 

Related Article

New Gene-Editing Technique Makes Strides Towards HIV Resistance

According to the Centers for Disease Control (CDC), 1,155,792 people in the United States have been diagnosed with acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). HIV targets T-cells via the CCR5 gene receptor which serves as a channel for the virus into cells. The virus then replicates inside the T-cells, eventually killing the host cells. This destruction of T-cells ultimately results in a highly susceptible immune system.While countless research projects aspire to develop a cure for the devastating virus, an approved cure has yet to be determined. However, hopes for finding a cure remain as vast strides towards a cure have been accomplished by some promising research.

Using a new gene-editing technique, researchers for the Harvard Stem Cell Institute (HSCI) at Massachusetts General (MGH) and Boston Children's (BCH) hospitals have created an effective technique for blocking HIV from invading and destroying its subject's immune system. The researchers effectively and precisely used CRISPR-Cas gene-editing technology to edit clinically relevant genes out of human hematopoietic stem cells and T-cells. The team was able to remove the CCR5 gene receptor out of of hematopoietic stem cells and demonstrate that these cells could differentiate into functional blood cells without the CCR5 gene. This outcome suggests that gene-edited stem cells could be delivered into HIV patients by bone marrow transplantation. The procedure would result in an HIV-resistant immune system. Dr. David Scadden, co-director of HSCI, stated that the new work is "a tremendous first step in editing out what makes human cells vulnerable to HIV."

The team identified areas of caution regarding the future of the new gene-editing therapy such as unexpected complications with the new therapy and the potential difficulty involved in treating people in the areas where HIV is most prevalent.The team also believes the new therapy will be ready for human safety trials within 5 years. The new therapy will undergo animal trials, and once they are completed, the team will apply for phase I human trials.

The more I read about the advances in gene-editing techniques, the more I am humbled at how far medical technology has come in such a short time period. I am excited to follow the development of this therapy through its trials. Advances such as this will encourage hope globally regarding the devastating virus.                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
 Article: http://news.harvard.edu/gazette/story/2014/11/a-promising-strategy-against-hiv/
Related Article: http://www.nejm.org/doi/pdf/10.1056/NEJMoa0802905

Extended Remission for Leukemia Patients

Every year in the United States about 2,400 people older than 20 are affected by acute lymphoblastic leukemia with only 40% cure rate and around 1,170 adults who die from it whereas 3,600 people under the age of 20 get affected by acute lymphoblastic leukemia with 80% cure rate and 270 who will die from it. Dr. Stephan A. Grupp, Dr. Carl H. June, and other researchers at the Children’s Hospital of Philadelphia (CHOP) have found an experimental treatment which uses patients’ own T-cells. T-cells are extracted then genetically engineered using a disabled virus to slip new genetic material into the cells. This genetic material reprograms the T-cells to identify and kill any cell that carries a specific protein on its surface. Once that happens the cells are dripped back into the patient. These cells are also encoded to multiply so they can produce as many as 10,000 or more cancer-killing cells.

The specific protein that is searched for is CD19 which is found on B-cells. This was chosen because the type of leukemia patents have affects the B-cells. Therefore, the T-cells are trained to destroy the B-cells. Since there is no way that cancerous B-cells can only be killed the healthy B-cells also have to be killed.

The usual treatment for acute lymphoblastic leukemia is stem cell transplant so some researchers believed to be on the safe side of any patient who went into remission after this T-cell treatment should also undergo stem cell transplant. Dr. June and Dr. Grupp suggested that due to the long remission the stem cell transplant might not be needed and that the T-cell treatment could hopefully replace the stem cell transplant.

Although this treatment sounds astonishing, T-cell treatment has its own side effects. T-cells churn out hormones called cytokines that can cause patients to have fevers, aches, drops in blood pressure, and trouble breathing. This is known as cytokine release syndrome. It is said that that more cancer there is to destroy the worse the syndrome.

The research trial Dr. June and Dr. Grupp did included 30 patients which 7 of the patients died who completed remission and then relapsed and 3 of the patients had the leukemia come back in B-cells that lacked the target protein which made them not vulnerable to the treatment.

Clearly this research doesn’t work for everyone but it is innovating in that in today’s world we can find cures for certain diseases and cancers. Although this is helpful for some patients this is only a research for the acute lymphoblastic leukemia and the researchers should find out why those seven patients died and come up with a method in how they can find who could be a perfect candidate for this research.  

Article: http://www.nytimes.com/2014/10/16/health/leukemia-patients-cell-therapy-childrens-hospital.html?mabReward=RI%3A17&src=rechp&WT.nav=RecEngine&module=ArrowsNav&contentCollection=Health&action=keypress&region=FixedLeft&pgtype=article

Butyric Acid Increases Amount of Treg Cells in the Gut

A recent  research conducted by RIKEN Center for Integrative Medical Sciences found that butyric acid, a by-product of fiber digesting bacteria which lives in the gut of humans, can actually boost the immune system. According to an article published on Science Daily, the butyric acid - a fatty acid- accomplishes this by epigenetically causing immature T- cells in our gut to mature into Treg cells.

Moreover, scientists have found that people who have a deficiency of butyric acid in their gut are more susceptible to and often do suffer from inflammatory bowel diseases.
Clearly this is a great discovery for not only the science community, but also for those who suffer from this disease. Because of the knowledge gained as a result of this research, we can understand the causes of inflammatory bowel diseases and also work towards treating them.

Cell Therapy Shows Promise for Acute Type of Leukemia

An experimental treatment that genetically alters a patient’s own immune cells, or T-cells, to fight cancer has produced remissions in adults with a deadly acute leukemia. This type of blood cancer is worse in adults than in children, the cure rate in adults is about 40 percent, compared with 80 to 90 percent in children. The experimental treatment uses a patient’s own T-cells, a type of white blood cell that normally fights viruses and cancer. The patient’s T-cells are extracted and genetically engineered using a disabled virus as a vector to carry new genetic material into the cells. The altered T-cells recognize and kill any cell that carries protein CD19 on its surface. CD19 is found on B-cells, which are part of the immune system. The patients in the study had a type of leukemia that affected B-cells, so the goal was to train the patients’ T-cells to destroy B-cells. Healthy B-cells would be killed along with cancerous ones, but that side effect is treatable.

Patients, who have relapsed after chemotherapy, usually have only a few months left. Three of the five patients that took part in this study have been in remission for 5 to 24 months. Their prognoses were good, but relapse was still possible, only time will tell. One patient from this study, 58 year old David Aponte was left in remission eight days after receiving the experimental treatment. Before any treatment Aponte agreed to his oncologist, Dr. Brentjens, suggestion that before starting chemotherapy Aponte have some of his T-cells removed and stored because chemotherapy would deplete the T-cells and he would no longer have the option to take part in the experiment if he were to relapse. After relapsing he joined the study. For the first few days nothing was happening. Then, his temperature began to rise, his fever spiked to 105 degrees. His T-cells were in a violent battle with the cancer and were churning out enormous amounts of hormones called cytokines. What was taking place is called a cytokine storm. The hormonal rush caused his blood pressure to plunge and his heart rate shoot up. Mr. Aponte was treated with steroids to subdue the reaction and eight days later, his leukemia was gone. After remission he was given a bone-marrow transplant, the normal and most promising treatment for this disease. Experts consider this treatment a highly promising approach for a variety of lethal cancers, including other blood cancers and tumors in organs like the prostate gland.

http://www.nytimes.com/2013/03/21/health/altered-t-cell-therapy-shows-promise-for-acute-leukemia.html?ref=geneticengineering