A Monoclonal Antibody Drug to Know: Herceptin

Herceptin (trastuzumab) is a fairly new monoclonal antibody that has changed the game in breast cancer treatment. But what exactly is a monoclonal antibody? Monoclonal antibodies are harvested from clone cells, and recognize the same epitope of an antigen because they all have the same variable and constant regions. To create a monoclonal antibody, usually an antigen is injected into an animal, such as a mouse. The mouse’s immune system will activate and proliferate B-cells for the antigen, but will die within generations. To combat the short lifespan, they are fused with myeloma cells, which can grow indefinitely but cannot make antibodies. Both B-cells and myeloma cells die, and the result of the fusion are hybridoma cells, which carry the antibodies needed against the antigen from the B-cells, and the indefinite proliferation of the myeloma cells. The antibodies are then harvested and are called monoclonal cells! What can be more cooler than that? It’s a monoclonal antibody that helps stop breast cancer!

Herceptin acts on the HER2 receptors, which is coded by a gene called HER2. Some breast cancer cells over-express this gene, causing the cancer cell to produce too many HER2 receptors on its cell surface and therefore stimulating cell growth. Herceptin binds to the HER2 receptors, blocking the signals for the cancer cell to growth and multiply. It also tags the cancer cell to let the immune system know that it it a cancerous cell and should be destroyed. This drug ultimately slows or stops the growth of breast cancer.

Side Effects of Herceptin:

  • Fever
  • Feeling sick to your stomach (nausea)
  • Throwing up (vomiting)
  • Infusion reactions
  • Diarrhea
  • Infections
  • Increased cough
  • Headache
  • Feeling tired
  • Shortness of breath
  • Rash
  • Low white and red blood cell count
  • Muscle pain

These side effects relate to how the drug is acting on the HER2 receptors of cancer cells. The immune system is trying to eliminate the cancer cells tagged by the drug. It may be suppressed because of the effort to try to eliminate and repair damaged cells, causing these side effects.

Herceptin can make an individual susceptible to infections such as Herpes Simplex infections, Urinary Tract infections and sepsis. The body’s immune system is suppressed when trying to eliminate the cancer cells, and at the same time is trying to elicit an immune response such as inflammation, increase temperature and a low blood pressure from leaky capillaries that may become too dangerous because of how overworked the immune system is. The innate immunity system is being impacted by Herceptin. Not only is it binding to the the receptors, but it is also tagging it, which will activate the classical pathway of the complement system as well as resident macrophages and PMNs. This response negatively affects the innate immune response because it is trying to restore balance and eliminate cancer cells that shouldn’t be there. Herceptin is surely a drug that everyone should learn about!

Your Immune System v.s Covid-19

During this pandemic, many of us are frightened out of our minds that we may not get sense of the whole thing. Do we actually know anything else about Covid-19 other than the fact that it’s a virus that is currently causing a human pandemic? Today, I’m here to spread some more knowledge about the virus, particularly about antibody responses against it. But first, let me give you some insight on what antibodies are what what they do! Antibodies are proteins that your immune system makes in order to fight an antigen. Our B-cells produce antibodies to specific antigens found on foreign substances such as bacteria or viruses, and lets the rest of the body know that there is an invader to fight off.

During an antibody response to Covid-19, the body first recognizes pathogen associated molecular patterns, or PAMPS, of the virus and this can include things such as the viral RNA genome. This first initiates the innate immune system, and then lets the adaptive immune system know when to start fighting. This involves the rapid proliferation of B-cells and T-cells with an antibody specific to the antigen of Covid-19. Specifically, IgM and IgG are produced. IgM is the first antibody to be produced at the start of an infection, and IgG helps protect against bacterial and viral infections.

IgM titers is a test used to measure the amount of IgM produced, having only a positive IgM titer means that the body has just been first introduced to the virus, and is trying to fight it off. IgG titers are the same thing, but measure the amount of IgG produced, and having only a positive IgG titer means that the body has previously been infected with the virus, and is not fighting it off (with memory B cells and T cells from the last infection). To have both means that the body is in the process of fighting the new infection and is trying to mount an adaptive response to it. If we could determine who was IgG positive, then it would mean that there could be a vaccine! With isolating the person’s antibodies for Covid-19, we could potentially create specific antibodies that would be effective for the virus; this would especially help those who are severely ill with Covid-19. This would also mean that the person would be immune to it, and prevent them from spreading the virus to others since they would not have the ability to infect others if their body has the ability to fight it off.

One last important fact about Covid-19 that everyone may not understand: everyone needs to try to quarantine themselves if they are able to. Isolating ourselves from others will not only save lives (particularly the elderly and those who are immunocompromised), but will also help get our lives back to normal faster. Stay healthy!

CAR T-Cell Therapy: A Promising Treatment

Lately there have been many terrible things happening in the world (as explained in my last post), but here’s some positivity to uplift everyone’s spirits: T-cell therapy. This is something that i have just learned about that has actually put me in a positive attitude about what’s happening in the world. T-cell therapy is the genetically engineering of T-cells. They are genetically changed so that they will attack a specific protein because of their modified T-cell receptors. In this post, I will specifically talk about chimeric antigen receptor (CAR) T-cell therapy.

First of all, what the heck is a T-cell? T-cells are white blood cells of the immune system and can kill the bad cells. CAR T-cell therapy is a type of cancer therapy that utilizes a patient’s white blood cells; they are genetically modified to target and kill the cancer cells. How does this work? First, a process known as leukapheresis is started, this is when the cancer patient’s blood is drawn and T-cells are separated from the blood (with the blood given back to the patient afterwards). The separated T-cells are genetically modified in a laboratory to have special receptors, call chimeric antigen receptors, that specifically target antigens on cancer cells. Once they recognize the cancer cells, they can become activated and kill them. Once they are modified, they are grown until an efficient amount is produced, and given returned back to the patient after they have received chemotherapy (to increase the chances that the body will accept the CAR T-cells.) This whole process sounds promising right? It definitely is, we all dreamed of a cure to cancer and this just take sit one step closer to it. However, there are some downfalls.

One of the downfalls is that this treatment has been effective in some types of cancer, not all, and CAR T-cell therapy does not always work because many patients relapse afterwards. Another downfall is that this treatment can be costly, something that many cannot afford. It costs about $373,000 per infusion, however many doctors have explained that this treatment has more promising results than just chemotherapy itself. CAR T-cell therapy comes with side effects such as cytokine release syndrome (similar to flu symptoms), neutropenia (low white blood count), anemia (low red blood cell count), confusion, aphasia, drowsiness, agitation, and brain disease or brain injury. Despite these downfalls, I believe that this is still a promising treatment, it takes us one step forward in the medical field which is very exciting. CAR T-cell therapy was first approved in 2017, and lots have been improved and discovered since then about this treatment. Who knows, it may 100% effective for all cancers in the future and be the first cure to it!

A “Great” Start to 2020

To be honest, I would have never expected to experience global pandemic that would impact life, but here I am. At the end of 2020, I had made a new year’s resolution to myself that I would get my life together and well… that didn’t exactly happen. Here I am quarantined in my house with all of my dorm life packed snugly into my room. I DREAMED of an extended spring break to hopefully mentally prepare myself that I have yet another half of a semester I still needed to finish before I finished my sophomore year at UNC, but now I am dreading it. Why? everything literally came crashing down on the whole world at once! First I hear that there’s a virus going around, the world isn’t too worried about it. Next thing I know this virus known as “Covid-19” or Ms. Rona as Twitter seems to call it, is spreading rapidly so fast that it is putting countries on lockdown and closing businesses everywhere. Don’t get me wrong, this is a very serious virus that everyone should be cautious about, but it is definitely taking a toll on my life. Here’s how:

It all started when people started buying out all of the toilet papers, as well as milk, eggs and packs of water bottles from the stores, completely emptying the aisles. Then, I get an email saying that universities are closing and are moving to online classes for the rest of the semester. For a person who lives with many brothers and a stay at home dad, it isn’t easy for me to study efficiently at home. I’ve been asked numerously by the media and my parents to stay at home and isolate myself, which was what I have been doing and it is currently driving me crazy because an extrovert like myself needs social interaction! I then get an email from my restaurant job saying that I have been laid off due to Covid-19, and I’m thinking, “great, how will I be able to make money?”. The same thing happens to my mom, who owns her own nail spa. At this point I’m completely scared about what will happen; how will we pay rent? How will I pay for my college tuition? I will we pay for groceries and other necessities? All of these questions are running through my head, the U.S definitely has not prepared for the consequences of this pandemic and we are painfully suffering from it.

I honestly believe that this is the start to the end of the world. 2020 has started with Australia being engulfed in bush fires for many months, volcanoes in the Philippines that have not had any activity in the last century are suddenly erupting and destroying villages, Locusts have swarmed East Africa, Indonesia has been flooding, Kobe Bryant died, and the coronavirus has became a global pandemic interrupting the lives of everyone. For now, one of our biggest problems, the coronavirus, is increasing in cases everyday and killing thousands. The world has always been so fast-paced, and it is probably the first time in history that it is not. Most people are practicing social distancing and staying in their homes instead of going out. I guess one of the positive things to come from this is that the environment is becoming “healthy” since pollution is decreasing due to lack of humans working and going out. This situation definitely reminds me of a movie called “Contagion” directed by Steven Spielberg, Warner Bros. , 2011. Will it end like it? Let’s hope so.

Nytimes.com

Backwards Progression in STDs: Syphilis

The number of syphilis cases has rose to an all time high in 2019 with 115,000 cases, a 14% increase since the highest record of 35,000 cases in the late 1900s. Many of these cases have affect mothers and babies. This STD can affect the reproductive health of women, causing infertility as well as ectopic pregnancies. With congenital syphilis, which is the passing of syphilis form mother to baby, consequences such as miscarriage, stillbirth, death, and sever lifelong neurological and physical problems can occur. Luckily, there are antibiotics that can cure syphilis, but why are we seeing an epidemic?

Syphilis is a common STD that is often asymptomatic, making it hard to catch early for treatment. Symptoms include painless sores on the vulva and vagina of women and on the penis and scrotum of men as well as the anus and mouth. Many also experience flu-like symptoms as the disease progresses. Syphilis testing is available for diagnosis, and is often treated with antibiotics such as penicillin. Factors that have distributed to the increase incidences include poverty, drug-use, stigma, decreased condom use, unstable housing, as well as HIV. I believe that all of these factors are preventable, it is really the government as well as society beliefs that is at fault for the increase of syphilis.

Programs can be implemented to educate the population, especially the youth, about practicing safe sex with condoms. Programs for helping the impoverished community can also be implemented for job security, which will also lead to housing security. As a society, I think that we should not stigmatize STDs so that individuals can openly seek help and treatment instead of letting it go unseen and possibly spreading it to others causing consequences for their own child. This will especially help individuals who already have an existing STD, such as HIV, because they are more susceptible to other STDs. Taking responsible in preventing syphilis is not only good for the population overall, but also for newborns who suffer the consequences of mothers with syphilis. Overall, the syphilis epidemic is a very preventable event that we can stop with support.

Antibiotic Resistance: The “Solution” Is Now The Problem

Since the discovery of antibiotics, many infectious pathogens were conquered and thus have saved many lives. However, what used to be the solution to our problem, has now become a new problem. Strain of pathogens are now becoming resistant to most antibiotics used to treat them, and are what we call “superbugs”. To break it down, superbugs come to be because of natural selection; mutated bacteria that are able to survive antibiotics reproduce while the others are killed from the antibiotic. Many factors contribute to this growing problem including clinical misuse, poor quality of available antibiotics, poor hospital-based antibiotic use regulation, lack of research on novel antibiotics, and antibiotic use in food producing animals in both developed and developing countries.

Antibiotic resistance, I believe, is a result of systemic capitalism and oppression. In the food industry, live stocks (sick or not) are fed the same antibiotics that we use for our infections for growth so that they can sold as large as possible for more money. Almost every animal consumed has been fed antibiotics, including ones that are said to be “antibiotic-free” because they have no antibiotics found in their blood only at the time of sale. These animals that are fed antibiotics because of the greediness of corporations are now contributing a great amount to emerging antibiotic resistance because the animals fecal matter can contaminate water and their products are being consumed essentially exposing the antibiotics to people who do not need it. An emerging antibiotic resistant strain of Camyplyobacter jejuni is example of antibiotic use in food animals, whose main transmission is through animals and uncontaminated water.

It is not just antibiotic use in livestock, but also misdiagnosis in clinical settings and low-quality antibiotics, especially prevalent in developing countries because of their lack of trained healthcare professionals and economic instability. Patients are given the wrong antibiotics for their illnesses, and are essentially given poor quality antibiotics that either makes them sicker or uncured. What will happen if we lose the ability to use antibiotics? This may sound unrealistic because of how fast-growing our health care system has been, but it is the harsh truth of reality. I think that the global mortality and morbidity rate would increase, and billions of dollars would be spent trying to find more antibiotics to use on super bugs. A strain of tuberculosis has already become multi-drug resistant (MDR-TB), and basically has no cure because every first and second defense antibiotics are useless towards it. If we are not careful about how we regulate our antibiotics, super bugs would soon take over and we will soon have no chance against them.

How Close Are We To #PolioEradication?

Poliomyelitis is a devastating disease that is caused by poliovirus. The virus infects the cells that line the throat and intestinal tract, and can spread and infect the central nervous system and cause paralysis. It may seem like an “old” disease that no one ever gets, but it is still circulating in countries who may not not the best vaccination options. The western hemisphere has completely eradicated polio, and the countries that still have cases of polio are Afghanistan and Pakistan; which I believe may be due to political conflict and internal tension within the countries causing people to not be vaccinated. However, there have been recent outbreaks in countries such as the Philippines, China, Myanmar and many African countries caused by vaccine-derived type 2 polio. I believe that these outbreaks could simply be ended with funding and better group efforts.

There are 3 serotypes of poliovirus: type 1, 2, and 3. As of October 24 (national polio day) , type 2 and 3 have been eradicated globally, leaving type 1 to be the only wild type to be circulating. There are two different vaccinations for the polio vaccine that help cause the immune system to produce antibodies against the virus: inactivated polio vaccine (IPV) and oral polio vaccine (OPV). OPV is an attenuated vaccine, which means that the it contains weaken strains of the virus and replicates in the cells that become infected, providing a better mucosal immunity than IPV. IPV is an inactivated strain that does not replicate within the cells, and has to be given in multiple injections over the course of several years; I think that this option is more privilege for people living in wealthy countries because they have better health care systems and have the ability to take time off and receive these vaccinations. Now that you got all the information on the disease and the vaccinations, let’s get to the reason on whats causing these outbreaks.

Even though wild type 2 polio has been eradicated, vaccine-derived type 2 cases have been increasing; 104 cases as of 2020 to be exact. OPV is mainly the cause for this because the attenuated vaccine has the ability to mutate because of it is able to replicate. Undeveloped countries are the main users of this vaccine because OPV is easier and cheaper to give, it is given orally one time so there is no need for highly-trained volunteers to be giving this vaccine out multiple times to one person . Not only this, but OPV can also flow throughout the environment from vaccinated patients; people who have not been exposed to the virus can be exposed to it this way and obtain polio. Researchers have created a new OPV vaccine that does not contain the type 2 strain to stop the administration of type 2 when it is not needed, which is the reason why type 2 has popped up again. Overall, there have been increasing amounts of efforts in the areas where vaccine-derived type 2 polio cases have been seen. This is just one small setback to the ongoing world wide mission on #PolioEradication!

The Scary “Good” Truth About What’s Inside of Us

The microbiome is a community of microorganisms, and are found throughout the body such as the skin, respiratory tract and gut. You may be familiar with one of largest ones within our body, the microbiome in the gut. Here lives many microorganisms, both bad and good. The “good” microorganisms actually help us in many ways, such as synthesizing vitamins, aiding in digestion, and competing in competition with bad pathogens. I think that many people have a bad perception on microorganisms, I mean, who wouldn’t? Everywhere in the media you hear about all of these diseases and infections that are becoming more prevalent because of these bad pathogens that you can’t even see and are becoming resistant to antibiotics. But what they don’t talk about are the good ones that actually live in huge numbers inside of you, and that make up basically what you are today.

There have been many studies that have proven that the microbiome has been linked to certain diseases or infections. For example, dysbiosis within the gut may cause irritable bowel syndrome, and studies have shown that with using fecal transplantation, which is the transferring of fecal matter from a healthy person to an unhealthy person with irritable bowel syndrome, the normal flora will replace the pre-existing microbiome within the diseased person and “cure” their irritable bowel syndrome. Studies within animal microbiomes have also helped us learn more about the relationship between our own microbiomes and other parts of he body. Many animal studies have strengthened the link between microbes and mental health such as depression, which gives us a better understanding of the importance of the microbiome’s role is within our body. Just like how the microbiota can help us, it can also potentially harm us if we do not properly treat it with care.

One study had explained the increasing global prevalence of chronic upper airway inflammatory respiratory diseases such as chronic rhinosinusitis and allergic rhinitis. Dysbiosis within the nasal microbiome due to increase usage of antibiotics and a high-fat low-fiber diet are mainly the causes to these prevalence, and a restoration of a healthy nasal microbiota can reverse it. Commensal upper respiratory microbiota has been reported to have beneficial effects for health, such as “removing or inhibiting pathogens, enhancing epithelial barrier integrity by the modulation of signaling pathways, and controlling local and systemic host immune responses” . Probiotics have been looked at to restore dysbiosis so that the beneficial functions of the good micoorganisms can continue. The usage of probiotics involves the oral intake of live organisms that can contribute to the healthy microbiome. In taking probiotics, patients with the above diseases find themselves improving their epithelial barrier integrity as well as their symptoms and signs, due to the competition the bad pathogens have to face with the good microorganisms.

Overall, microorganisms aren’t just “bad” for us. We have many communities within our bodies full of microorganisms, with the majority of them actually helping us in defining our overall health and preventing diseases and infections.

The “Guessing” Game with the Flu

If you don’t know anything about the flu, heres a quick summary:

The flu is caused by influenza viruses that infects the nose, throat and lungs. It is a contagious respiratory illness that can spread through droplet nuclei from infected people when they talk, sneeze or cough, which I think makes the flu dangerous because it can easily be contracted. It is a common illness that many people get, and it is easily preventable with annual vaccinations. People with the flu may experience sudden onset fever, coughs, chills, sore throat, chills, and muscle or body aches and many more. Even though this is a common illness, there is no definite vaccine that can cure all influenza viruses.

Flu epidemics are occurring every year because the virus can change every year by acquiring mutations in their surface proteins haemagluttinins and neuraminidases, which help name the flu viruses . These surface protein mutations allow the virus to enter the immune system more easily if the person does not have the right vaccination against it because the immune system does not have the appropriate receptors for the virus, and therefore cannot bind to them. I believe that this virus’s ability to become highly changeable is not only dangerous for the human population, but it has also helped us learn much more about viruses and vaccinations, so it’s not all bad with the flu! But let’s get to the real question here: how effective is the flu vaccine every year?

During seasons when the flu virus in well matched to the flu vaccine, flu cases decrease between 40%-60%. This is also due to the fact that if you had had the flu, you are better immune to whatever strain you had because you have memory B cells that recognize that certain strain. However, influenza is constantly changing, and even though we have excellent predictions on the what flu virus is going to come this year, there are some factors that affect the effectiveness of the vaccine such as age/health and the similarity between the flu virus the vaccination is protecting from and the circulating flu virus within the community. The flu vaccine is highly effective, reducing deaths as well of hospitalization of children and adults, however not for the elderly. The vaccine is highly effective for two stains of the virus, Influenza B or A (H1N1) but not Influenza A (H3N2) because it that certain strain is even more unpredictable since it is changing at a more aggressive rate that we cannot predict a well-matched vaccination for.

Even though the flu virus is changing every year, the CDC (which conducts studies to predict the appropriate vaccine to use every year), makes/predicts effective vaccinations that are beneficial either way. I suggest everyone to get the flu vaccine every year, it will definitely prevent unwanted sickness and time off from work or school if you have the unfortunate chance of acquiring the sickness. If you do find yourself with the flu symptoms. make sure to stay home and get some rest! There is no cure for the flu, there are medications to help with symptoms, and the sickness should last approximately 7-10 days! Make sure to also cover your mouth, since these pesky invaders can easily spread through the air.

Andrew Wakefield: #AntiVaxxer

In 1998, Andrew Wakefield had started a worldwide controversy pertaining to the safety of the MMR vaccination. The MMR vaccination is a 3-in-1 vaccination for measles, mumps and rubella that was first introduced to the United Kingdom in 1998; the same year Wakefield had voiced his concern for this vaccine. Wakefield and his 12 cohorts from the Royal Free Hospital in London, UK, had published their findings in the paper “The Lancet” on 12 children who all had bowel syndrome, in their study. Wakefield and his colleagues had found evidence of a link between the measles virus and autism and/or bowel syndrome. He had proposed at a press conference that the MMR vaccine was unsafe, and that children should individually get vaccinated for measles, mumps, and rubella, even though his colleagues were against this proposal.

There has been no actual observed data on the link between the MMR vaccine and autism/bowel syndrome, or that individual vaccines are safer. Vaccination rates in the United Kingdom had fallen from 98% to 80% after his publication. Multiple well-known organizations have actually written rebuttals on Wakefield’s hypothesis saying that there is no link and that his proposal to give three separate vaccines is unsafe because it leaves children to the diseases longer in order to change the public’s opinion. Many have argued that Andrew Wakefield had other motives for publishing this paper. It was revealed that he had patented his own single-antigen vaccines for the diseases, giving the public a reason to think that Wakefield had financial motives.

In response to measles, mumps, and varicella infections and vaccinations around the world, public policies have been introduced to advocate for adequate funding of public health systems and for higher vaccination rates. There have been many outbreaks in areas, such as the recent outbreak in Vancouver, Canada, that could have easily been preventable if children were given vaccinations at the appropriate age that they should have been vaccinated. Parents who do not vaccinate their children are often faced with the challenge of receiving health insurance, or are easily biased by media coverage presented by #AntiVaxxers. The United States have since worked with schools as well as physicians in order to make sure children are protected at a young age from mumps, measles and varicella not only to prevent the occurrence of disease in themselves, but to also protect others from the disease within the community.