March 11, 2019(updated March 11, 2019) Published by Kshitij Kumar
In a recent study, it was proved that immunotherapy drug ‘pembrolizumab‘ responds better than conventional chemotherapy, in case of skin cancer ‘Markel cell carcinoma’, a type of skin cancer.
Merkel cell carcinoma (MCC), is a rare and aggressive type of skin cancer, can be treatable if caught early. Tumors often respond to chemotherapy by shrinking, but only for a short time after which they start growing again.
Merkel cells are located in the outermost layer of the skin and are primarily known as touch receptors. Merkel cell tumors majorly begin on sun-exposed parts of the body, such as face and neck. Their shape and color are less distinctive than other skin cancers, so people usually only notice them after a long time because of rapid growth. It occurs in older people and those who have weak immune systems.
Nearly 80 percent of Merkel cell carcinomas are caused by a virus called the ‘Merkel cell polyomavirus‘. The disease is diagnosed in 1,500 people each year in the United States, and in about 10% of those people, it has already spread.
Photomicrograph of Merkel cell carcinoma infiltrating the skin (arrow). Tumor cell nuclei are stained brown by an antibody to the Merkel cell polyomavirus large T antigen. (Image: Patrick S. Moore/ Wikipedia)
For initiating this study, investigators from the Bloomberg-Kimmel Institute joined hands with researchers from the Fred Hutchinson Cancer Research Center in Seattle, along with 11 other U.S. medical centers. The Bloomberg~Kimmel Institute team comprise Topalian, William Sharfman, M.D., Evan Lipson, M.D., Abha Soni, D.O., M.P.H., and Janis Taube, M.D., M.Sc.
The study, initiated by Suzanne Topalian, M.D., associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, is the longest observation to date of Merkel cell carcinoma patients treated with any anti-PD-1 immunotherapy drug used in the primary treatment.
The research, published in the Journal of Clinical Oncology, supported the recent (Dec. 19, 2018) U.S. Food and Drug Administration approved of pembrolizumab, marketed as Keytruda, as a primary treatment for adult and pediatric patients with advanced ‘Merkel cell carcinoma’.
The study was conducted over 50 patients with pembrolizumab who had recurrent, locally advanced or metastatic Merkel cell carcinoma. More than half of the patients i.e 28 patients (56 percent) had long-lasting responses to the treatment, 12 people (24 percent) experienced a complete disappearance of their tumors. About 70 percent of patients were alive for two years after starting the treatment.
“This has been such an encouraging development for this disease. When I first started treating people with Merkel cell carcinoma at MSK, the only thing I had to offer them was chemotherapy, and I knew how limited the benefit would be. It is great to have immunotherapy that’s available to block tumor growth and potentially allow people to live longer.”, said Memorial Sloan Kettering medical oncologist Sandra D’Angelo.
Researchers said treatment with pembrolizumab worked well against both virus-positive and virus-negative Merkel cell carcinomas, resulting in high response rates and durable progression-free survival in both subtypes. The research showed that tumors expressing a PD-1-related protein called PD-L1 were likely to respond longer and better to the treatment, although patients whose tumors did not express PD-L1 also responded.
Study says that patients who respond to immune therapy tend to continue their responses for longer time span. Unfortunately, 28 percent of patients experienced serious side effects, including death.
A man from London is being said to be free from the AIDS virus. The person, known as the “London patient”, had leukemia and underwent a stem cell transplant to treat cancer. The donor’s cells had a protein which is supposed to combat the HIV virus.
Timothy Ray Brown, from the USA, was the first man who was treated in Germany and is originally known as the “Berlin patient”. He is still free of HIV even after 12 years of the treatment. Until now, Brown was the only person known to have been cured of infection with HIV, the virus that causes AIDS.
Brown is the only person in the history who went through two successful stem cell transplants and when asked about the same, post this second victorious treatment, he said, “I knew I was the only person cured of HIV at that point and I didn’t want to be the only person“.
How does it work?
CCR5 is the most commonly used receptor by HIV to enter the cells. But a very small number of HIV resistant people have two mutated copies of the CCR5 receptor, called delta-32 mutation. This mutation stops the virus to penetrate cells in the body that it normally infects.
The London patient received stem cells from a donor with this specific genetic mutation, which made him resistant to HIV as well. But even after the treatment, cells carrying HIV can still remain in the body, in a resting state, for many years.
The Doctors’ verdicts:
According to the doctors, treatments like stem cell transplant are difficult, dangerous and have failed in other patients. They’re also impractical to try to cure the millions of people worldwide who are infected with HIV.
“The latest successful operation shows that the cure of Timothy Brown was not just a matter of chance or luck and can be repeated”, said Dr.Keith Jerome of Fred Hutchinson Cancer Research Centre in Seattle. He added that it could generate a simpler formula that could be used more widely.
Dr. Rowena Johnston, who oversaw the research at the Foundation for AIDS Research, said that this is a really exciting news.
Dr. Anthony Fauci, the person who is in charge of government HIV research, cautions: “This approach is unsafe, unsuitable and not scalable”, meaning it could not be replicated among many patients. But, he points out that it may have pertinence in future attempts to use gene editing to treat AIDS.
The latest patients are part of a research project which has so far enrolled 45 patients with cancer and HIV, who have received or will receive stem cell transplants.
February 5, 2019(updated May 26, 2019) Published by Kshitij Kumar
Immune systems are made up of various WBC or White Blood Cells with several tissues and organs. The main job of the immune system is to fight against germs and microorganisms and keep the body healthy. Immunotherapy drugs aid the immune system to work well, and that makes it easier for the body to get rid of certain cancer cells.
Immunotherapy helps to slow down the growth and flow of cancer cells. It restricts cancer to spread in the body and helps the immune system to respond well by destroying the cancer cells. There are numerous immunotherapy drugs explicitly tested in labs, which can fight cancer.
Immunotherapy can have major side effects. If you are being advised for immunotherapy by your doctor, then there are a lot of reasons to talk about them before you decide to go for this curing process. Immunotherapy is known to be a cancer treatment which can boost your body’s natural defenses to fight against cancer, but it can also make them rogue which may end up attacking healthy, functioning parts of a person’s body, causing unpredictable side effects that may be life-threatening if not treated early.
All you need to know about Immunotherapy
There are numerous treatments such as chemotherapy, surgery and radiation which are widely approved as the standard way of treatments to stop cancer. Many additional drugs are utilized to restrict the growth and spread of cancer cells. Treat your side effects which arise due to radiation, surgery, and you can manage the pain. Moreover, the traditional cancer treatment can kill several diseases where the patient’s body is under attacked by different diseases. However, it is sometimes dangerous, exhausting, and its side effects are explicitly substantial.
The idea and the new treatment have caught several attentions of doctors and scientists. The results for different patients are credible. And it is known as Immunotherapy, and the goal is to boost your immune system to stop cancer. Those who are interested in the medical field of immunotherapy recognize the main power of the human body. According to the sources and researches, it has been found that the immune system can eliminate the tumors on a patient body by simply co-opting inhibitory pathways. Thus it put a break on the response of the immune system. The idea of immunotherapy includes the engineering, or it enhances the immune cells of the patients that wipe out the cancer elements.
The therapy is also known as ACT (Adoptive Cell Transfer), and its clinical results are simply remarkable. Remain cancer free by simply eliminating the cancer cells and improve your health. Experts clearly agree to the fact that the human immune system can do well if the right amount of tools is provided to it.
Immunotherapy is classified as a ‘Living Drug.’
Immunotherapy is known as the ‘living drug’ because it is responsible for building the T-cells. A patient’s blood collects these, and the cells are further altered to build “special receptors” which are referred to CAR’s or Chimeric Antigen Receptors. Basically, these CAR’s are the protein which allows these T-cells to strikes the antigen-protein which is found in the cancer cells.
The T-cells are then engineered in the lab which is simply allowed to grow in billions. These T-cells are injected inside the patient, and hence the T-cells reproduce to soak out the antigens and damage them. First, the T-cells experimentation was begun in the late 1990s, and the researchers considered it as the new cancer treatment. And today, the scientists and the researchers are finding many different ways for generating new yet powerful T-cells which can eliminate the cancer cells from a patient’s body.
How the concept of Immunotherapy works?
The T-cells protects your body from getting infected, and hence they destroy the infected cells.
As you know, cancer cells produce the molecules that stop the T-cells and helps cancer to grow in your body.
The drug gets attached to the T-cells and blocks the cancer cells. The T-cells continuously attacks and destroys the cancer cells. And meanwhile, the ipilimumab helps the T-cells to multiply.
What are the benefits of Immunotherapy?
There are many great benefits of Immunotherapy, and it’s a good choice for patients to get rid of cancer diseases. There are many cancers such as skin cancer which doesn’t respond to chemotherapy and radiation. But the use of immunotherapy has helped the patients to eliminate the cancer cells.
The T-cells are largely grown in the laboratory and then it is injected inside the patient’s body, and hence your body performs well. Hence, immunotherapy is classified as the broad category that is designed to stimulate the immune system of your body for better recognition and fighting cancer.
Some side effects of Immunotherapy
The ACT simply causes bothersome effects which are referred to as Cytokine- a release syndrome. The T-cells that are engineered eliminates the cytokines- which are the chemical messengers which help T-cells to complete their mission. A large number of cytokines in your bloodstream can cause low blood pressure and high fever.
Many of the patients have experienced syndrome, and on the other hand, some have reported only mild side effects. Researchers and scientists are putting their best efforts to improve the ACT process so that it can be used as a standard process for the treatment of cancer.
Most of the drugs have delayed the spread of cancer but unable to cure the cancer disease. Your immune system is designed in such a way that it couldn’t destroy or attacks your own cells. The immunotherapy is not being used for a long period, and it is a long hope that the immunotherapy drugs can teach the body to destroy the cancer cells.
Later, cancer will be banished, and you will be enjoying your healthy life in the coming years. And it is truly an exciting idea for patients who are suffering from cancer diseases. These researches show that the patients can give a powerful one or two punch against these virally infected diseases.
February 5, 2019(updated July 26, 2019) Published by Kshitij Kumar
CRISPR and the CRISPR Associated system are powerful gene-editing technologies.
For the scientists, the genes and its related fields have been an area of interests for research for a number of years. They have found a lot of therapies and treatments where modern technologies are used to cure various diseases as well as preventive treatments. The DNA(Deoxyribonucleic acid) is the system of the human body with the help of which one can study the genes and decipher many things that can be used to treat various diseases that happen to an individual. Among these studies, the leading one is CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) that have originated before few decades. CRISPR was first described by Osaka University researcher Yoshizumi Ishino and his associates in the year 1987. They accidentally duplicated part of a CRISPR together with the “iap” gene which was the original interest.
Genome editing is a group of methods that gives researchers the ability to modify the DNA of an organism. These technologies let genetic substance to be added, detached, or transformed at specific locations in the gene. Several methods to genome editing have been advanced. The latest one is recognized as CRISPR-Cas9.
CRISPR Cas9 – Mode of Action. Image Source: Wikipedia
Cas9 (or “CRISPR-associated protein 9“) is an enzyme that uses CRISPR DNA sequences as a guide to recognize and cleave specific strands of DNA that exactly match given CRISPR sequence, it is so precise in matching DNA that Cas9 can be called as a GPS locator of DNA. Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR-Cas9 that can be used to edit genes within organisms.
Companies like Synthego provide Full Stack Genome Engineering. You can go check out their website for various offers.
CRISPR technology is a modest yet influential tool for excision genes. It lets researchers alter DNA arrangements and modify gene function effortlessly. Its many possible applications include modifying genetic defects, giving and averting the spread of diseases and refining crops.
This system has produced a lot of enthusiasm among the researchers and scientists because it is quicker, inexpensive, more precise, and more well-organized than other prevailing methods for genome editing.
CRISPR-Cas9 from Nature
CRISPR-Cas9 was adapted from a naturally happening gene editing process in bacteria. Whenever viruses attack bacteria they inject there own code of DNA into the bacteria and if the bacteria survives this attack, it stores the virus’s DNA in a DNA archive called CRISPR. When the same virus or any virus of the same strain attacks the bacteria again, the bacteria quickly produces an RNA from the stored DNA and uses the Cas-9 protein to scan through to find the exact match of virus DNA. If it does find a match, it removes that DNA protecting the bacteria from the virus.
The CRISPR-Cas9 scheme works likewise in the lab. Examiners create a small portion of RNA with a short “guide” arrangement that attributes (binds) to a precise target arrangement of DNA in a gene. The RNA also muddles to the Cas9 enzyme. As in microbes, the adapted RNA is used to identify the DNA arrangement, and the Cas9 enzyme punctures the DNA at the battered location. Even though Cas9 is the enzyme that is used most frequently, certain other enzymes like Cpf1 (CRISPR-associated endonuclease in Prevotella and Francisella 1) can also be used. Once the DNA is cut, investigators use the cell’s DNA repair gear to add or delete pieces of inherited material or to make variations to the DNA by substituting prevailing section with a tailored DNA sequence.
The human DNA model takes on a double helix shape. Source: www.pixabay.com
Gene editing is of inordinate importance in the inhibition and treatment of the human ailment. Presently, most study on genome editing is done to comprehend diseases using cells and animal models. Researchers are still at work to define whether this method is harmless and operative for use in people.
Use of CRISPR in different fields
Now let us look into some other potential uses of CRISPR which can be revolutionary:
1) Genetically editing crop seeds for higher yields and higher nutrition: Researchers are doing various experiments with crop seeds and CRISPR. They are trying to develop resistance against diseases in crops. Companies have been licensing CRISPR technology to develop new varieties of crops.
2) Using CRISPR to prevent and cure deadly diseases: It is being discovered in the investigation on a wide diversity of ailments, as well as single-gene complaints such as cystic fibrosis, haemophilia, and sickle cell disease. It can also prevent more complex diseases, such as HIV, Zika, Cancer, Heart Disease, Mental illness. Apart from prevention, scientists claim that we can even cure diseases like HIV. We can even develop effective antibiotics (which are becoming ineffective day by day) against an increasing number of superbugs.
3) We could alter an entire species: CRISPR has the potential to alter a complete species. This concept is called Gene Drive. Generally, whenever organisms mate there is a 50-50 chance to pass a particular gene but using CRISPR we can make a particular gene to pass with nearly 100 percent probability. This can be pretty beneficial if we use it properly, for example, we can totally prevent Malaria by genetically editing mosquito.
Regulating gene drives, Biotechnology journal, Javier Zarracina; Oye et al. 2014
Moral concerns do ascend during the editing of genome, using technologies such as this one, is put to use to make changes in human genes. Most of these variations are known with gene editing and are incomplete to somatic cells, which are cells other than egg and sperm cells. These deviations affect only definite tissues and are not conceded from one age group to the next. However, alterations made to genes in egg or sperm cells or the genes of an embryo could be distributed to future groups. Embryo genome and germline cell editing are developed with numerous ethical trials, including the probabilities if same can be permitted to use this technology to improve normal human traits like height or intelligence. Centred on apprehensions about integrity and wellbeing, germline cell and embryo gene editing are at present illegal in many nations.
Though CRISPR has a lot of potential, it also has a lot of controversies around it. Many researchers claim that CRISPR could cause extensive mutation and gene damage which could not be easily detected.
A Chinese scientist named He Jiankui created the first ever genetically edited twin babies. He also edited one more baby with the twins. The Chinese government stated that he has violated Chinese rules and has avoided supervision, faked an ethical review, and used potentially unsafe and ineffective gene editing methods on the children. This created a lot of controversies around CRISPR in early 2019.
Even after that, there have been reports from various parts of the world describing controversial and unethical CRISPR research. There are reports saying that researchers have edited the genes of healthy embryos which is illegal and have created controversies.
In between all this, we have also got bio-hackers who can create potentially harmful micro-organisms using CRISPR as this technology is available to anyone and is easier compared to other gene editing technologies. So, we have to monitor CRISPR usage and watch potential bio-hackers to save humanity from some gene edited deadly microbes.
CRISPR has the potential to make completely altered human beings which can be dangerous in many ways. So, there is are many rules in force against the use of CRISPR in almost all countries. But still, there is a possibility that someone could misuse this technology.
Advantages of CRISPR over other Gene Editing Methods
Questionably, the most imperative rewards of CRISPR-Cas9 over other genome editing technologies is its uncomplicatedness and effectiveness. To give a good comparison if old methods are like maps then CRISPR is like a GPS system. CRISPR/Cas9 is way faster and decreases the time required to perform a gene edit to a few days from a few months or even years. CRISPR gene editing is way cheaper than other gene editing technologies.
An unwanted reaction in the immune system might occur.
Wrong cells may get targeted if we are editing specific cells in grown-up organisms.
There is a possibility of infection.
The new segments may get inserted in the wrong spot leading to unwanted and dangerous changes.
There is a lot of buzz around CRISPR and gene editing and if used properly can give good results otherwise can be harmful to humanity. There must be National and International Organisations strictly monitoring gene editing research and any trial of biohacking must be strictly punished. Things apart, let us hope that CRISPR gets established and we get fruits of it early in the form of disease prevention, cure, good crops etc.
February 5, 2019(updated May 27, 2019) Published by Kshitij Kumar
Herd immunity (Herd protection): A Visualization of How Herd Immunity Works
Populations of various species have always strived to thrive on this magnificent planet of ours. Survival of a species is imperative to maintain the balance on this planet. During outbreaks of diseases and infections that can prove detrimental to the population, it is absolutely necessary that the population develops immunity towards the disease or infection. This immunity can be a result of vaccination or internal conformities to the changes that take place naturally. What if I told you that immunity to the population can be assured through immunity developed in only a section of the population? This is claimed to be possible and is referred to as herd immunity.
Herd immunity is a form of immunity where an entire population or community becomes immune to an infectious disease due to immunity achieved by a large section of that population or community. Although several scientists have tried to prove that the theory of herd immunity is a fallacy, there has not been substantial evidence that suggests that herd immunity is not a real thing. So, what is herd immunity? How does herd immunity work? How can communities achieve herd immunity? If these questions intrigue you and pique your interest, then stick around to find out more.
When more people are immunized, the lesser number of people there are that are susceptible to attaining the infectious disease. The spread of the disease is largely controlled in such scenarios. When no one in the community is immunized, the chances of the infectious disease spreading are extremely high. When a few people are immunized, the chances of contracting the disease reduces. When most of the population is immunized, the chances of contracting the disease reduces further.
When a sufficient proportion of the community or population is immunized, the spread of the disease within the community or population can be completely ceased. This provides immunity to the entire population/community. This form of immunity is the herd immunity.
To develop a thorough understanding of the concept of herd immunity, we will first need to understand immunity.
Chart Flow Diagram Depicting The Divisions Of Immunity . Image Source: Wikipedia
Immunity is derived from the Latin word, immunis, meaning exemption. Immunity is the state of the organism that enables it to combat infections, diseases, and other biological invasions. An individual would have to develop the appropriate defenses against the infection or disease to be deemed immune from that disease or infection.
Innate and adaptive components of an immune system
The innate components of immunity include the bone marrow cells. These innate components are designed in such a way that they produce certain reactions to foreign substances. These reactions could be rashes, bumps, inflammations or even non-visual.
Innate immunity is the result of an individual’s genetic make-up. The resistance due to innate immunity can be resistance to all diseases in general, or, resistance to a particular microorganism only.
The adaptive components of an immune system include lymphatic cells. These cells do not react to foreign substances. They do not produce any reaction. Adaptive immunity could be natural or artificial. Natural immunity is the conformity to the infection or disease in such a way that it is no longer as harmful. Artificial immunity results from deliberate actions such as vaccination.
Passive and Active immunity
When antibodies from an individual are transferred to another resulting in the immunity in the individual that receives the antibodies, then the receiving individual is said to have acquired passive immunity. Passive immunity can be naturally or artificially acquired.
Natural passive immunity is acquired when the antibodies are transferred from the mother to the fetus. This transfer generally happens when the baby is developing inside the mother’s womb in the gestation period. These antibodies are referred to as Maternal antibodies (MatAb). This transfer is said to occur usually in the third month of gestation.
Artificial passive immunity is the result of the transfer of antibodies from an immunized person to a non-immune individual. This is carried out by transferring human or animal blood plasma to the infected individual.This form of immunity is generally ephemeral. It does not last forever. This form of countering infections has been used for an extremely long time even before the advent of antibiotics.
Passive immunity could also be acquired through transfer of T-lymphocytes or T-cells. However, this form of transfer is rarely seen in humans.
Active immunity is the response developed against the pathogens by the body due to previous interactions with the pathogens. When B-cells and T-cells are activated, they form memory B-cells and memory T-cells. These cells remember pathogens and develop mechanisms to counter them the next time around.
Natural active immunity is acquired when an individual develops an immunological memory to the pathogen. This memory allows the individual to develop a response that can fight the micro-organisms better.
Artificial active immunity is generally induced due to the administration of vaccines. These vaccines need to be administered through physical means.
Vaccines are biological preparations that aim to combat microorganisms that cause infections and diseases. The process of administering these vaccines is called vaccination. Vaccines can be used to alleviate the effects of the infection, or, can be used to cure the infection.
Types of vaccines
Inactivated vaccines consist of micro-organisms that are dead during the administration of the vaccine. These micro-organisms would generally have been destroyed through treatment with heat, chemicals, or radiation.
These vaccines consist of live, attenuated micro-organisms. These micro-organisms generally consist of live active viruses that are cultivated. They generally lack virulent properties and are used to combat the micro-organisms that cause the infection. Different non-contagious strains of micro-organisms are used for this purpose.
Toxoids generally do not use micro-organisms. Instead, toxoids use activated toxic compounds. Toxoids are known to be extremely efficient.
Sometimes, a fragment of a micro-organism is used to treat infections. This fragment is the protein subunit.
How does herd immunity work?
Now that we have understood immunity, let’s get back to the concept of herd immunity. Like I have mentioned, if there exists a large enough number of individuals in a community that is immunized or vaccinated, it means that even some non-immunized or non-vaccinated individuals of the community gain immunity. If there are too few individuals who are vaccinated or immunized, the concept of herd immunity would fail.
This concept is extremely useful.This protects even the unvaccinated section of the community. The reason that this is so useful is that there is the possibility that some of these individuals are allergic to vaccines. Individuals could also have autoimmune disorders that prevent them from taking up the vaccination. Often, individuals won’t have access to the vaccinations. In all these scenarios, herd immunity comes to the rescue.
The equation for herd immunity is given by:
qc = 1 – (1/Ro)
qcis the critical immune threshold and Rois the number of individuals that one can infect, Ro is a measure of how transmissive a disease is.
For example, if the number of individuals that one can affect is 8, then the value of qc is given by:
1 – (1/8) = 1 – 0.125 = 0.875
This means that 87.5% of the population needs to be immunized in order to achieve herd immunity in a community where an individual can affect eight other people.
There has long been a discussion on whether vaccines are causing more harm than benefit. But, there should be no doubt that they are necessary.Measles is a disease that can, on average, affect 15 other people when an individual contracts it. In other words, it is highly contagious. Enough vaccination against measles can help eradicate it. Measles can only survive and reproduce in a host cell. That is why measles is known to enter human beings. An individual infected with measles has a 90% chance of infecting an individual that is not immunized to it. For prevention of such contagious diseases, herd immunity is crucial. Despite all the debates against vaccines and vaccination, it would be ridiculous to not vaccinate against diseases especially when they are as contagious as measles.
Bill Gates, who is the principal founder of Microsoft and once the richest man in the world once said, “Treatment without prevention is simply unsustainable”. Treatment for a disease can only be made possible through a comprehensive effort to prevent it. To carry out the preventive measures, it is necessary for us to make an integrated effort to vaccinate against the diseases. Diseases are the bane of the society and have continuously tormented the human race from time immemorial.
In the fight against these deadly assailants that we call diseases, a systematic approach of vaccination and immunization needs to be carried out. The brilliance in the concept of herd immunity can enable better standards of living for human beings. Herd immunity can ensure that humans truly thrive. Through herd immunity, we can fight diseases and infections that have been detrimental. Smallpox has been eradicated and the concept of herd immunity has played its part in ensuring its eradication. Polio could be the next in line to be eradicated. Herd immunity could truly be revolutionary in our efforts of creating a clean and healthy world to live in.
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