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?
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," say 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 aluminum. 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 engineer 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 autoimmunity, 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."