Cancer, Infection, and Autoimmunity in 2018

Cancer, infection, and autoimmunity in 2018: Will we win the war?

Vaccines proved to be a game changer in modern medicine. The fight isn’t over yet, however; cancer, infectious diseases, and autoimmune conditions still plague humanity to this day. Might 2018 see the tipping point in this war?

Biomaterials can be used in a number of ways in the development of vaccines and immunotherapy.

Imagine a world in which vaccines are painless, could be applied in the comfort of your own home, and can even eradicate infectious diseases such as flu and HIV.

Think of immunotherapies that are specifically targeted to combat cancer cells, stop allergies in their track, and prevent organ rejection.

The secret to making this leap may potentially lie in innovative biomaterials, say Dr. Jonathan S. Bromberg, who is a professor of surgery and microbiology and immunology, and Christopher M. Jewell, Ph.D., who is an associate professor in the Fischell Department of Bioengineering, both at the University of Maryland in College Park.

Writing in the journal Trends in Immunology, Profs. Bromberg and Jewell take us through a journey into the fascinating world of biomaterials and the potential they hold to revolutionize vaccines and immunotherapy.

What are biomaterials?

A biomaterial is any type of material, whether natural or synthetic, that could be used in medicine to “[…] support, enhance, or replace damaged tissue or a biological function,” said the National Institute of Biomedical Imaging and Bioengineering, of the National Institutes of Health (NIH).

What does that mean? Biomaterials can hail from all walks of life. They come in the form of glass, ceramics, plastic, metal, and biological materials such as collagen and gelatin, and they can even be made from cells or organs.

Biomaterials can be made into large structures, such as hip joints, contact lenses, or stents, and smaller ones, including sutures and dissolvable dressings.

For the purpose of vaccines and immunotherapies, biomaterials have the advantage of being able to function at the microscopic level.

Profs. Bromberg and Jewell go on to explain, “Some of the broad classes of biomaterials include: (i) nanoparticles (NPs) and microparticles (MPs) formed from polymers or lipids that can be conjugated or delivered to immune cells; (ii) stable or degradable scaffolds for implantation; and (iii) devices such as microneedle arrays that target immune cells in the skin.”

While biomaterials are firmly entrenched in some areas of modern medicine — such as in the form of heart valves and implants — they are a relative late-comer to the field of vaccine and immunotherapy development.

Yet, Profs. Jewell and Bromberg point to their potential: better control over where and how quickly a vaccine is released, protection from enzymatic degradation or extreme environments such as stomach acid, and a way of manipulating how the immune system responds.

Fighting infectious diseases

When we think of vaccines, infectious diseases are likely what comes to mind. The majority of modern vaccines contain two elements: a part of the infectious microorganism or one of their antigens, and an adjuvant, which is a substance that activates the immune system.

The most commonly used adjuvant in vaccines is aluminium. But biomaterials themselves may soon feature as next-generation adjuvants, not just as mere delivery boys, because they themselves can elicit immune responses.

The multitude of biomaterials in development make this especially appealing; the shape, size, and chemistry of each specific material can be used to fine-tune the desired immunological response.

“Now we have an opportunity to have the carrier manipulate the immune system based on the structure, providing an additional route to engineering the most effective immune response,” explains Prof. Jewell.

For example, nanoparticles and lipids used to deliver an HIV vaccine in mice have shown improved immune responses, Profs. Bromberg and Jewell write.

“Another promising strategy recently entering the clinic,” they continue, “is delivery of vaccine components using microneedles.”

Microneedles are, as their name suggests, tiny needles that can be used to permeate the skin and deliver vaccines. As they are so small and do not penetrate very deeply, microneedles do not cause pain.

Using a dissolvable microneedle to deliver a vaccine against the flu virus in the first trial in humans showed that this technology achieved comparable results with a standard flu shot, even when study subjects applied the painless microneedle patch themselves.

As Profs. Bromberg and Jewell explain:

Such advances could transform the way vaccines are delivered, as well as the accessibility of effective formulations in developing regions. Not surprising, microneedles are also being explored as vaccines for HIV.”

Killing cancer cells

In cancer therapy, it is essential that a treatment homes in on its target. But this is easier said than done. How does a vaccine pick its way through our many organs and cell types to find the right spot?

Biomaterials can help in a number of ways.

They can be primed with a homing signal, such as a molecule that is specific to a cancer cell. This will allow the biomaterial to dock onto a cell bearing the matching molecule — like a lock and key — and deliver a chemotherapy to kill the cancer cell. By killing only the target tumor cells, the side effects of chemotherapy may be significantly reduced.

Biomaterials could also make use of the body’s own ability to fight against cancer cells. And, by binding biomaterials to immune cells — specifically, T cells that recognize cancer cells — studies show that it is possible to improve a T cell’s innate anti-tumor response.

Meanwhile, microneedles can be used to deliver molecules into the skin to prime the local T cell population to fight malignant melanoma, the most aggressive form of skin cancer.

As Prof. Bromberg says, “This is a brand-new way of thinking about how, where, and when to deliver immune signals and antigens so you get a much better immune response.”

“It’s allowing some real paradigm shifts in thinking about vaccines for treating and preventing infectious disease,” he adds, “and also for potential vaccines for cancer.”

Keeping autoimmunity in check

Vaccines against both infectious diseases and cancer seek to harness a pro-inflammatory immune response. But the opposite is the case for conditions caused by autoimmunities, such as multiple sclerosis (MS), allergy, and organ transplant rejection.

Here, biomaterials can be used to suppress or redirect how the immune system behaves.

In experimental MS models, biomaterials have been used to deliver self-antigens or antigens to which only people with autoimmune conditions normally react, in order to shift the immune response from attack to tolerance. In mice, this led to improvements in symptoms.

The treatment of allergies with allergy shots is already well-established. However, many forms of allergy immunotherapy require frequent injections — up to three times per week during the initial phase — and can take several years to complete.

By encapsulating the active substances in biomaterials, scientists are now looking to create slow-release versions of the therapeutics. This would negate the need for frequent shots and may also reduce side effects and improve how the immune system responds, Profs. Bromberg and Jewell write.

For Prof. Bromberg, the prospect of preventing organ transplant rejection is particularly intriguing. Slow release formulations of immunosuppressants, specifically designed to control the levels of inflammation that occur after organ transplantation, have shown promising results in mouse transplant models.

The vaccine and immunotherapy war in 2018

“Despite the past advances of vaccines and immunotherapies,” write Profs. Bromberg and Jewell, “there is an increasing need for greater control over the types of immune responses generated to combat infection, cancer, and autoimmunity.”

Of course, there is work still to be done.

Few therapies have been tested in humans. Precisely how our immune systems will react to biomaterials will have to be studied in more detail before the war against cancer, infectious diseases, and autoimmune conditions will be won in our favor.

Profs. Bromberg and Jewell conclude by saying:

Still, biomaterials allow better control over responses to antigens, adjuvants, or immunomodulators and can be used to target these cues to particular tissues or cell populations, or to modify immune cells or pathogens.”


Eight Potential Health Benefits of Kombucha

Kombucha is a sweet, fizzy drink made of yeast, sugar, and fermented tea. It has a number of potential health benefits, including gut health and liver function.

This article explores eight potential health benefits of kombucha and looks at the research that supports them.

What is kombucha?

A jar of raw kombucha fermented drink, on a wooden table with chopped up lemon and a stem of ginger.
Kombucha is a fermented drink that is popular for its purported health benefits.

To make kombucha, sweetened green or black tea is fermented with a symbiotic colony of bacteria and yeast, otherwise known as a SCOBY.

During the fermentation process, the yeast in the SCOBY breaks down the sugar in the tea and releases probiotic bacteria.

Kombucha becomes carbonated after fermentation, which is why the drink is fizzy.

Potential health benefits

There is a range of potential health benefits of kombucha, including:

1. Gut health

As this 2014 study confirms, the fermentation process of kombucha means that the drink is rich in probiotics. Probiotic bacteria are similar to healthful bacteria that are found in the gut.

Consuming probiotics may improve overall gut health. Probiotic bacteria have been found to help treat diarrhea, and some research suggests they may help ease irritable bowel syndrome(IBS).

More research is needed into how kombucha improves gut health, but the link between probiotics and gut health suggests it may support the digestive system.

The link between healthy bacteria in the digestive system and immune function is becoming clearer as more studies focus on gut health. If the probiotics in kombucha improve gut health, they may also strengthen the immune system.

2. Cancer risk

There is growing evidence to suggest drinking kombucha could help reduce the risk of cancer.

2008 study found that kombucha helped prevent the growth of cancer cells. Further research in 2013 found that kombucha decreased the survival of cancer cells. Both studies suggest kombucha could play a role in treating or preventing cancer.

It is important to note that these studies looked at the effects of kombucha on cancer cells in a test tube. More research is needed to see if people who drink kombucha have a reduced risk of developing cancer.

3. Infection risk

A type of acid called acetic acid, also found in vinegar, is produced when kombucha is fermented.

study carried out in 2000 found that kombucha was able to kill microbes and help fight a range of bacteria. This suggests that it may help prevent infections by killing the bacteria that cause them before they are absorbed by the body.

4. Mental health

Young smiling woman drinking fruit juice ice tea.
The probiotics in kombucha are thought to have the ability to treat depression.

There may be a link between probiotics and depression, suggesting that drinking probiotic-rich kombucha could help promote positive mental health.

There are strong links between depression and inflammation so the anti-inflammatory effect of kombucha may help alleviate some of the symptoms of depression.

2017 review looked at a number of existing studies and concluded that there is strong evidence that probiotics may help treat depression. However, further research is needed to prove how effective they are.

5. Heart disease

Levels of certain types of cholesterol increase the risk of heart disease. Studies in 2012 and 2015 found that kombucha helps to reduce levels of the cholesterol linked to heart disease. Cholesterol levels and heart disease are also influenced by diet, exercise, weight, lifestyle habits, and inflammation. However, the research cited here suggests drinking kombucha may help reduce the risk of heart disease.

At the same time, it is important to note that these studies were in rats. More research is needed to prove that kombucha reduces the risk of heart disease in humans.

6. Weight loss

When kombucha is made with green tea, it may aid weight loss. A 2008 study found that obese people who took green tea extract burned more calories and lost more weight than those who did not.

If kombucha is made with green tea, it follows that it could have a similarly positive effect on weight loss.

Again, researchers need to look at kombucha and weight loss specifically before this is certain.

7. Liver health

Kombucha contains antioxidants that help fight molecules in the body that can damage cells.

Some studies, the most recent being in 2011, have found that the antioxidant-rich kombucha reduces toxins in the liver. This suggests that kombucha may play an important role in promoting liver health and reducing liver inflammation.

However, studies to date have looked at rats and more research is needed to say with certainty how kombucha can support liver health in humans.

8. Type 2 diabetes management

Kombucha tea in iced bottles, with fruit segments fermenting.
Kombucha may help to stabilize blood sugar levels and aid in the management of diabetes.

Kombucha may also be helpful in managing type 2 diabetes.

2012 study found that kombucha helped to manage blood sugar levels in rats with diabetes. This finding suggests it may be helpful in type 2 diabetes management.

Again, more research is needed to say with certainty whether kombucha can have the same benefits in type 2 diabetes management for humans.

Are there any risks?

It is important to be careful when making kombucha at home, as it can ferment for too long. It is also possible for kombucha to become contaminated when not made in a sterile environment.

Over-fermentation or contamination may cause health problems so it may be safer to buy kombucha in a store than to make it at home.

Store-bought kombucha normally has a lower alcohol content than homemade versions, but it is important to check the sugar content.

There are many potential health benefits of kombucha. However, it is important to remember that research is ongoing and not all benefits have been proven in studies with human participants.

If made properly or bought in-store, kombucha is a probiotic-rich drink that is safe to enjoy as part of a healthful diet.

Chewing Your Food Could Protect Against Infection

“Chew your food!” This is a phrase likely to have been heard by many of us during childhood. According to a new study, we would be wise to take that advice. Researchers have found that chewing food prompts the release of an immune cell that can protect against infection.
[A lady eating a salad]
Chew your food; it could help protect you from illness.

The study, recently published in the journal Immunity, found that chewing food – otherwise known as mastication – can stimulate the release of T helper 17 (Th17) cells in the mouth.

Th17 cells form a part of the adaptive immune system, which uses specific antigens to defend against potentially harmful pathogens while enduring “friendly” bacteria that can be beneficial to health.

According to the study team, led by Dr. Joanne Konkel of the University of Manchester in the United Kingdom, in the gut and the skin, Th17 cells are produced through the presence of friendly bacteria.

However, the researchers note that the mechanisms by which Th17 cells are produced in the mouth have been unclear.

Chewing ‘can induce a protective immune response in our gums’

Dr. Konkel and colleagues note that the mechanical force required by mastication leads to physiological abrasion and damage in the mouth.

With this in mind, the team set out to investigate whether such damage might play a role in oral Th17 cell production.

The researchers came to their findings by feeding weaning mice soft-textured foods, which required less chewing until they reached 24 weeks of age. At 24 weeks, the release of Th17 cells in the rodents’ mouths was measured.

A significant reduction in oral Th17 cell production was noted, which the team speculated was down to a reduction in mastication-induced physiological damage.

Confirming their theory, the researchers found that increasing the levels of physiological damage in the rodents’ mouths – by rubbing the oral cavity with a sterile cotton applicator – led to an increase in the production of Th17 cells.

Dr. Konkel and colleagues believe these findings indicate that chewing food may help to protect us from illness.

“The immune system performs a remarkable balancing act at barrier sites such as the skin, mouth and gut by fighting off harmful pathogens while tolerating the presence of normal friendly bacteria.

Our research shows that, unlike at other barriers, the mouth has a different way of stimulating Th17 cells: not by bacteria but by mastication. Therefore mastication can induce a protective immune response in our gums.”

Dr. Joanne Konkel

The downsides of excessive mastication

However, the researchers caution that increased oral Th17 cell production may not always be beneficial; too many of these cells can increase the risk of periodontitis, or gum disease, which has been associated with numerous other health conditions, including diabetes and rheumatoid arthritis.

In their study, the team also found that long-term exposure to physiological damage caused by mastication can exacerbate the effects of periodontitis.

They came to this finding by feeding weaning mice hardened food pellets up until 24 weeks of age.

Compared with mice fed soft food, the mice fed hard food showed more mastication-induced physiological damage in their mouths and increased periodontal bone loss.

Still, the researchers believe that their findings could lead to new strategies to combat an array of illnesses.

“Importantly, because inflammation in the mouth is linked to the development of diseases all around the body,” says Dr. Konkel, “understanding the tissue-specific factors that regulate immunity at the oral barrier could eventually lead to new ways to treat multiple inflammatory conditions.”