Immunotherapy to cure Cancer

From the huge discovery of Cancer therapy by American and Japanese immunologists:  James P Allison and Tasuku Honjo who were awarded Nobel Prize in Medicine for their research, research remains relentless in the cancer cure domain of health science and medicine.

The recent publication in Nature by National Cancer Institute researchers have described a novel immunotherapy approach which showed nil tumor presence in an advanced metastatic breast cancer surviving patient who just 2 months to live. The research work mentioned that the naturally-occurring tumor infiltrating lymphocytes (TILs) were extracted from the patient's tumor, grown outside of her body in larger numbers and injected back into the patient to tackle the cancer. While the TILs are grown externally patient is treated with PD-1 blocking, immunotherapy agent Keytruda to modify the immune system so that other immune cells wouldn’t interfere with the TILs upon injection into patient.

This novel approach of immunotherapy involves 2 steps first being Sequencing DNA of the tumor cells and second being the TILs extraction, analysis, growth and injection. The TILs will be analyzed for their ability to recognize and target the mutated proteins on the tumor. Researchers have been enthusiastic about applying TILs for treatment of common epithelial cancers which include those of the colon, rectum, pancreas, breast and lung.  Rosenberg, one of the researchers claimed that: “These treatments have the potential to treat patients with any cancer”. Though this immunotherapy approach for personalized cancer treatment seems promising and better compared to radiotherapy and chemotherapy the only worry is the resistance.

Cancers often develop resistance to treatments and the resistant cancer cells may have different mutations than the original tumor. Picking TILs that target just a single or small number of mutated proteins on the tumor may increase probability of cancer resistance. Identification of which mutations on cancer cells are possible targets for TILs must be researched. Hence more funding and trials is to be considered. Industries often shy away due to the expenses and the market but there are some companies Bristol-Myers Squibb and Iovance Biotherapeutics who are up for the risk and specifically focus on TILs.

What are your thoughts in regards to immunotherapy? Is it really that promising? Let us know by submitting us your ideas or research in form of an abstract at: Abstract Submission. Interested to be part of this fascinating ideas networking event at Abu Dhabi? Then write to us at allergy@mehealthevents.org

Gene Silencing Technology

Year 2018 welcomes the novel family of FDA approved drugs for inherited diseases. These drugs which are backed by a Nobel Prize and 2 decades of research have the ability to cure inherited diseases without actually editing the delicate genome. It is said that they are powerful enough to give a backseat to CRISPR based gene therapy. One such drug is “Patisiran” developed by biopharmaceutical company-Alnylam for treatment of genetic nerve damage. It works on RNA interference (RNAi) technology.

As we all know that DNA along with messenger RNA (mRNA) produces proteins via transcription and translation process. RNAi does the work of shooting down the messenger and erasing the message for protein production. Scientists believe that this will be greater method for treatment of inherited genetic or immune disorders than gene therapy or immunotherapy. Gene therapy involves cutting out the mutated gene region and replacing it with the new gene but this tampering may have certain risks like ethical regulations, unspecific gene region cut and unpredicted changes in gene silently leading to cancer activation. However RNAi ensures that no bad disease is developed and no bad protein is produced by shooting down the compilation of the message by mRNA.

RNAi not just works on inherited diseases but also on non-inherited diseases like stroke too. In Stroke, group of proteins get activated together to kill the brain cells. RNAi can stop such activation thus protecting the brain cells. Sometimes even good proteins can turn bad upon being faced by any pathogenic situation leading to a disease. As RNAi are reversible when compared to gene therapy, RNAi can be used to silence the proteins temporarily in such circumstances and restore them back to their normal functional state after the change in situation.      
                                                      

So the question arises. If function of RNAi is really that great and it was discovered long back in 1998, what’s stopping this RNAi or RNA technology developed drugs to enter the market? It seems that the production in this technology is easy but the real problem lies in targeting and delivering the therapy to the specified tissue in question. RNAi works by addition of small snippets of synthetic nucleotides which homes the RNAi, delivers it to the disease-causing RNA to silence it. The problem that arises is host immune system gets triggered upon the introduction of these nucleotide snippets in the body and the activation can lead to massive inflammation and even death. To avoid the immune system risk these snippets can be coated in nanoparticles but they will just end up in liver or kidney thus making the RNAi treatment difficult to reach brain, heart or lungs.

Patisiran was successful and approved by FDA for treatment of rare disease called hereditary transthyretin-mediated amyloidosis (hATTR) by targeting the liver itself. The drug doesn’t encounter the delivery problem as the drug wrapped in nanoparticles will be delivered to patients through infusion. As Alnylam Company is focused on the discovery, development and commercialization of RNA interference therapeutics for genetically defined diseases, this approval has given a huge leap for the company to go forward with the technology. The company is seen developing other RNAi-based candidate therapies that aim to treat high cholesterol, bleeding disorders, and Parkinson’s disease.

CD-8 cells to fight Cancer and Chronic Infections

Immune system has several components like cytokines, lymphocytes, macrophages etc. CD-8 cell is one major component produced by the host immune system to fight pathogens like bacteria, virus etc. Upon exposure to any invading pathogen like virus, CD8 cells multiply rapidly. At the initial stage they are effector cells, acting like foot soldiers and killing the pathogen. Once the pathogen is destroyed, most of these effector cells suicide to not continue attacking the body’s own cells. Few effector CD8 cells that survive become memory cells guarding the host from the respective pathogen and enacting faster combat reaction upon exposure to same pathogen.

 CAR T cell therapy gathered lot of attention from the public for its effective use in immunotherapy against cancer and chronic infections like HIV. Application of CD-8 cells in immunotherapy has been discussed recently. The usual problem encountered is that CD8 cells get exhausted or stop functioning properly in cancer and HIV infections.  However recent research by Shomyseh Sanjabi and her team have discovered a great finding which could offer a greater option against cancer and chronic infections.

The team identified 2 molecules namely Sprouty 1 and Sprouty 2. These molecules are known to modify the survival and development of effector and memory CD8 cells respectively. Upon animal model research, the team found that in absence of these molecules in CD8 cells, the CD8 effector cells survived in larger numbers and became memory cells. The memory cells without these molecules had better protective capacity against bacterial pathogens than normal CD8 memory cells with Sprouty molecules.

In tumors, as tumor cells consume lot of glucose the effector CD8cells get killed due to glucose deprive however the CD8 cells without Sprouty 1& 2 molecules can survive and function in a tumor environment upon consuming less glucose. Also the memory CD8 cells without Sprouty molecules can tackle cancer cells and also cells activated with latent virus in viral infections. Hence the memory plays a good role in immunotherapy and the future engineering of CAR Tcells in combination with genome editing technique like CRISPR can help in future to eliminate the Sprouty molecules and employ CD8 cells against cancer and infected cells.

To know more such research or present your findings in the field, write to us at allergy@mehealthevents.org or drop your interest at: Allergy 2018

Gene Therapy

The dysfunction of the immune system can cause immune disorders. The dysfunction factor might be hyper/hypo activity of the immune system, misregulation of any of the components constituting the immune system or a hereditary factor. Overall the immune disorders can be characterized into autoimmune diseases, immunodeficiency and allergies. Apart from Immunotherapy and vaccination, gene therapy also can be considered in treatment of some of these immune disorders.

Gene therapy is the experimental technique developed in 1972. The technique employs genes to treat and prevent diseases like AIDS, cancer, genetic disorders and rare diseases. The principle behind the technique can be in 3 ways:

• Introduction of new gene to a body to fight the disease.
• Replacing the disease caused mutated gene with healthy gene copy(Gene Editing)
• Knocking out the improper functioning gene( Gene Silencing)

Gene therapy is the only therapy which can be effective completely however several regulations, ethical considerations and market investments hinder the success of the therapy. Though the debate on the application of gene therapy still prevails, FDA has shown approval in some of the cases. In August 2017, FDA had given approval for a cancer therapy: CAR-T treatment marketed as Kymriah against leukemia. Another CAR-T treatment, marketed as Yescarta, was approved against non-Hodgkin’s lymphoma in October 2017. Since these cases didn’t exactly show the replacement or repair of gene, they were not truly the first cases of gene therapy.

The first US approval was for Luxturna developed by Spark Therapeutics, which is a 1-time treatment against rare, inherited blindness. Several clinical trials continue to test gene therapy options for genetic conditions, cancer and HIV/AIDS. Some of the diseases where gene therapy was a success was spinal muscular atrophy type 1 (SMA1) and junctional epidermolysis bullosa (JEB). Though several companies have trouble receiving complaints from ethical regulatory boards and also seeking investments for research and market of gene therapy products, the option to consider gene therapy for diseases and conditions which are horrific, deadly with no cure is always open.

Celiac Disease or Wheat Allergy

Throughout the globe, America comes first in allergy statistics followed by other countries. Among the several types of allergies, food allergies are most commonly faced. The food allergens may be eggs, sea food, nuts, milk, soy, gluten and so on. Gluten as we all know is a protein found in wheat, barley, rye and other grains. Though most people follow a gluten free diet, for people with celiac disease it is a must to follow the gluten free diet.

 Celiac disease also called gluten-sensitive enteropathy is an autoimmune disorder triggered by gluten.    Upon consumption of gluten, immune system of people with celiac disease attacks villi, which are the small finger like projections in small intestine responsible for nutrient absorption. Damage to villi and small intestine is seen in this disorder leading to malnourishment and lack of functioning. Several other symptoms of the disease includes abdominal pain, nausea, anemia, diarrhea, gas, constipation, mouth ulcers, weight loss, heartburn, headaches, fatigue, loss of bone density etc.

The intestinal problems are more common in children than in adults with symptoms like nausea, bloating, steatorrhea, weight loss, constipation and diarrhea. Celiac disease is not the same as food allergy specifically wheat allergy. If an individual is allergic to wheat, then upon wheat consumption he/she might have itchy watery eyes and hard time breathing whereas the symptoms in case of disease vary by a lot. It is observed that not everyone with the disease face all symptoms. As the damage to the intestine process is very slow and the symptoms vary by a lot, diagnosis becomes a huge task.

The treatment for the disease is also not available. The only option out there for people with the disease is to follow a gluten free diet and take precautions in their food habits. Living with allergies and autoimmune diseases is heavy task. Awareness, Caution and Prevention becomes the 3 life mantra words to live day-to-day life.

Allergy Epidemic from gel nail polishes!

Recently throughout Ireland and UK, an allergy epidemic has been reported and warned by the British Association of Dermatologists (BAD). The allergy epidemic is seen due to recent trends in gel and acrylic nail polishes. Meth acrylate chemicals are the key ingredients in acrylic nails, gel nails and gel polish nails and the study conducted last year in 13 dermatology units found that at least 2.4% people were tested positive for allergy against any 1 type of the Meth acrylate chemicals.

Among the 742 people attending skin clinics, 19% showed adverse effects from acrylic nails applied in salons and 16% suffered from allergic reactions to a salon gel polish treatment. The latest trend of gel and gel polish nail manicures use polishes which get hardened under UV light for a long lasting effect. Later on these gel nails are physically buffed off and soaked in acetone. In case of acrylic nail paste, air exposure and then acetone soaking is done.

The uncured chemicals from these substances can get in contact with skin and when this happens, sensitization occurs. It is thus important to understand that allergies can occur from artificial nails too. Allergic reactions can involve symptoms like nail loosening, rash and itchiness not just on fingernails but also on different parts of body which get in contact with nails. Rarely breathing problems are also encountered.

Though (Meth)acrylates are main components in acrylic plastics production and also employed in graphic and printing industry, aircraft manufacture, adhesives, orthopedic cement, dressings and dentistry; the fact that is alarming the BAD is their consecutive use in nail enhancement industry and increasing widespread exposure. Many women out there might be allergic but remain undiagnosed due to symptoms occurring in different parts of body like face, neck, genitals etc.

It is important to get diagnosed towards these chemicals so that they can avoid the allergen. Developing an allergy to these chemicals can be alarming as there will be lifelong consequences due to the fact that these chemicals are employed in surgeries and dental treatments. Hence awareness of the same is a must among general public, doctors and manicure specialists.

Are you really allergic to Penicillin?

Penicillin, the first and widely used antibiotic for treating several bacterial infections was first discovered by Dr Alexander Fleming. Fleming found out that Pencillium notatum has the capability to produce the compound for destruction of surrounding bacterial cells. The discovery led to production of penicillin antibiotics for wide applications in hospitals. The Penicillin synthesized by various species of the Penicillium mold can be of 2 types. One is the naturally occurring penicillin which is formed during the mold fermentation process and the 2^nd type is the semisynthetic penicillin which is synthesized by altering the structure of 6-aminopenicillanic acid found in all natural penicillin. The structure and characteristics of the antibiotic are changed to meet the desirable requirements like Oral medication, drug effectiveness and so on.

The mechanism involved is Penicillium produces the chemical compound penicillin upon facing danger from different microbes like Staphylococcus bacteria and so on. The compound inhibits the bacterial growth enzyme and also activates several enzymes required for cell wall breakdown. As a result, bacterial cells are killed. As human cells lack cell wall, penicillin is safe to be used. Well that’s what we assumed at the earlier days.

Now however, with the allergies on the rise against several antigens, penicillin allergy is one of the most common drug allergy witnessed by several people worldwide. Penicillin allergy is the reaction of the host immune system to the antibiotic drug penicillin. The common symptoms of the allergy include rash, swelling, hives, itching and so on. Severe reaction includes anaphylaxis, the life threatening condition which can affect several systems of the body and cause death. Penicillin and some other compounds with similar properties can cause the allergic reactions however some events i.e the side effects faced after intake of penicillin is misunderstood for allergies. Doctor consultation is a must to differentiate and realize whether the reactions are just adverse side effects or allergies.

Penicillin Allergy Evaluation must be appropriate as it can combat infections and reduce antibiotic resistance. It was observed that 95% of patients with penicillin allergy indication in medical records were truly not allergic and showed to have increased infection risk of MRSA (methicillin-resistant Staphylococcus aureus) and Clostridium difficile (C. difficile). Thus drug allergy must be done appropriately to overcome dangerous infections and antibiotic resistance which are huge public concerns.