- Scientists develop new design principles to improve vaccine structure and therapeutic outcomes for seven different types of cancer
- Breakthrough vaccine design principles significantly enhance the efficacy of checkpoint inhibitor in fighting aggressive melanoma in vivo
- Blueprint established for redeveloping all vaccines – including those for infectious diseases like COVID-19
EVANSTON, Ill. --- A new way to significantly increase the potency of almost any vaccine has been developed by researchers from the International Institute for Nanotechnology (IIN) at Northwestern University.
The scientists used chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine, greatly increasing vaccine performance. The antigen targets the immune system, and the adjuvant is a stimulator that increases the effectiveness of the antigen.
The study was published Jan. 30 in Nature Biomedical Engineering.
“The work shows that vaccine structure and not just the components is a critical factor in determining vaccine efficacy,” said lead investigator Chad A. Mirkin, director of the IIN. “Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it.
Mirkin also is the George B. Rathmann Professor of Chemistry at the Weinberg College of Arts and Sciences and a professor of medicine at Northwestern University Feinberg School of Medicine.
This new heightened emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which historically have not worked well, Mirkin said.
Mirkin’s team has studied the effect of vaccine structure in the context of seven different types of cancer to date, including triple-negative breast cancer, papillomavirus-induced cervical cancer, melanoma, colon cancer and prostate cancer to determine the most effective architecture to treat each disease.
Conventional vaccines take a blender approach
With most conventional vaccines, the antigen and the adjuvant are blended and injected into a patient. There is no control over the vaccine structure, and, consequently, limited control over the trafficking and processing of the vaccine components. Thus, there is no control over how well the vaccine works.
“A challenge with conventional vaccines is that out of that blended mish mosh, an immune cell might pick up 50 antigens and one adjuvant or one antigen and 50 adjuvants,” said study author and former Northwestern postdoctoral associate Michelle Teplensky, who is now an assistant professor at Boston University. “But there must be an optimum ratio of each that would maximize the vaccine’s effectiveness.”
Enter SNAs (spherical nucleic acids), which are the structural platform — invented and developed by Mirkin — used in this new class of modular vaccines. SNAs allow scientists to pinpoint exactly how many antigens and adjuvants are being delivered to cells. SNAs also enable scientists to tailor how these vaccine components are presented, and the rate at which they are processed. Such structural considerations, which greatly impact vaccine effectiveness, are largely ignored in conventional approaches.
Vaccines developed through ‘rational vaccinology’ offer precise dosing for maximum effectiveness
This approach to systematically control antigen and adjuvant locations within modular vaccine architectures was created by Mirkin, who coined the term rational vaccinology to describe it. It is based on the concept that the structural presentation of vaccine components is as important as the components themselves in driving efficacy.
“Vaccines developed through rational vaccinology deliver the precise dose of antigen and adjuvant to every immune cell, so they are all equally primed to attack cancer cells,” said Mirkin, who also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “If your immune cells are soldiers, a traditional vaccine leaves some unarmed; our vaccine arms them all with a powerful weapon with which to kill cancer. Which immune cell ‘soldiers’ do you want to attack your cancer cells?” Mirkin asked rhetorically.
Building an (even) better vaccine
The team developed a cancer vaccine that reduced tumor growth by >4 times compared to checkpoint inhibitor monotherapy, and led to a 40% extension in median survival.
By reconfiguring the architecture of a vaccine containing multiple targets, the SNA enables the immune system to find tumor cells. The team investigated differences in how well two antigens were recognized by the immune system depending on their placement — on the core or perimeter — of the SNA structure. For an SNA with optimum placement, they could increase the immune response and how quickly the nanovaccine triggered cytokine (an immune cell protein) production to boost T cells attacking the cancer cells. The scientists also studied how the different placements affected the immune system’s ability to remember the invader, and whether the memory was long-term.
“Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it,” Mirkin said.
The most powerful structure throws two punches to outsmart the wily, mutating tumor
The study data show that attaching two different antigens to an SNA comprising a shell of adjuvant was the most potent approach for a cancer vaccine structure. These engineered SNA nanostructures stalled tumor growth in multiple animal models.
“It is remarkable,” Mirkin said. “When altering the placement of antigens in two vaccines that are nearly identical from a compositional standpoint, the treatment benefit against tumors is dramatically changed. One vaccine is potent and useful, while the other is much less effective.”
Many current cancer vaccines are designed to primarily activate cytotoxic T cells, only one defense against a cancer cell. Because tumor cells are always mutating, they can easily escape this immune cell surveillance, quickly rendering the vaccine ineffective. The odds are higher that the T cell will recognize a mutating cancer cell if it has more ways — multiple antigens — to recognize it.
“You need more than one type of T cell activated, so you can more easily attack a tumor cell,” Teplensky said. “The more types of cells the immune system has to go after tumors, the better. Vaccines consisting of multiple antigens targeting multiple immune cell types are necessary to induce enhanced and long-lasting tumor remission.”
Another advantage of the rational vaccinology approach, especially when used with a nanostructure like an SNA, is that it’s easy to alter the structure of a vaccine to go after a different type of disease. Mirkin said they simply switch out a peptide, a snippet of a cancer protein with a chemical handle that “clips” onto the structure, not unlike adding a new charm to a bracelet.
Path to most effective vaccine for any cancer type
“The collective importance of this work is that it lays the foundation for developing the most effective forms of vaccine for almost any type of cancer,” Teplensky said. “It is about redefining how we develop vaccines across the board, including ones for infectious diseases.”
In a previously published paper, Mirkin, Teplensky and colleagues demonstrated the importance of vaccine structure for COVID-19 by creating vaccines that exhibited protective immunity in 100% of animals against a lethal viral infection.
“Small changes in antigen placement on a vaccine significantly elevate cell-to-cell communication, cross-talk and cell synergy,” Mirkin said. “The developments made in this work provide a path forward to rethinking the design of vaccines for cancer and other diseases as a whole.”
Northwestern Ph.D. candidate Michael Evangelopoulos also is an author of the paper, titled “Multi-Antigen Spherical Nucleic Acid Cancer Vaccines.”
Founded in 2000 as an umbrella organization to coalesce and foster nanotechnology efforts, the IIN represents and unites more than $1 billion in nanotechnology research, educational programs, and supporting infrastructure.
This study is based upon work supported by the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, Edward Bachrach and the National Cancer Institute of the National Institutes of Health (R01CA208783, R01CA257926, and P50CA221747). Teplensky also received support from Northwestern University’s Cancer Nanotechnology Training Program Award (T32CA186897). Evangelopoulos was partially supported by the Dr. John N. Nicholson Fellowship and the Alexander S. Onassis Public Benefit Foundation.
FAQs
How are cancer vaccines created? ›
Some cancer treatment vaccines are made up of cancer cells, parts of cells, or pure antigens (certain proteins on the cancer cells). Sometimes a patient's own immune cells are removed and exposed to these substances in the lab to create the vaccine.
What are cancer vaccines made of? ›DNA and RNA vaccines
These vaccines are made with bits of DNA or RNA that are usually found in cancer cells. They can be injected into the body to make the cells of the immune system better at responding to and destroying cancer cells.
Vaccines (Shots) The HPV vaccine can prevent several kinds of cancer, and the hepatitis B vaccine can help prevent liver cancer.
What are the two types of cancer vaccines? ›Vaccines to prevent cancer work by training the immune cells to recognize the virus. In the United States, the Food and Drug Administration (FDA) have approved two vaccines to prevent cancer: the human papillomavirus (HPV) vaccine and the hepatitis B vaccine.
What is the limitation of cancer vaccine? ›One of the major obstacles to effective cancer vaccine development is targeting of tumor antigens that may have low immunogenicity in the tumor environment or may mutate to evade the immune response.
How is cell based vaccine made? ›The cell-based vaccine manufacturing process uses mammalian cells (Madin-Darby Canine Kidney, or MDCK cells) to grow flu viruses instead of fertilized hen's eggs. For the 2022-2023 season, the CVVs provided to the cell-based vaccine manufacturer are cell-derived rather than egg-derived.
Have any cancer vaccines been approved? ›In April 2010 the US Food and Drug Administration approved a purpose made cancer vaccine for the first time. The sipuleucel-T vaccine, which goes by the brand name Provenge, uses a patient's immune cells and a protein from prostate cancer cells, the antigen, to stimulate the immune system.
How can you prevent cancer naturally? ›- Don't use tobacco. ...
- Eat a healthy diet. ...
- Maintain a healthy weight and be physically active. ...
- Protect yourself from the sun. ...
- Get vaccinated. ...
- Avoid risky behaviors. ...
- Get regular medical care.
The earliest vaccine can be traced back to 1796 when Edward Jenner found that the cowpox vaccine protects against smallpox infection [1]. As the vaccine developed, it was later introduced to treat more diseases, such as cancers. The initial cancer vaccine based on tumor cells and tumor lysates was developed in 1980.
Is there a DNA vaccine for cancer? ›Therapeutic DNA cancer vaccines are now considered a very promising strategy to activate the immune system against cancer. In the past, several clinical trials using plasmid DNA vaccines demonstrated a good safety profile and the activation of a broad and specific immune response.
Which type of cancer has been reported to prevent by vaccination? ›
Vaccines to prevent certain types of cancer already exist. They target viruses: hepatitis B virus, which can trigger liver cancer, and human papillomavirus, which causes cervical and some other cancers. But most cancers are not caused by viruses.
Why do cancer vaccines fail? ›Many such trials have ended in failure, which we now know is because these antigens muster only weak immune responses because they are normal human proteins merely overexpressed on tumor cells (to which the patient would be tolerant) or they too closely resemble such proteins or they elicit only a weak response from ...
What is the new cancer treatment injection? ›The novel therapy called Vaxinia can reduce the size of a broad range of cancers in animal and laboratory models at low doses. This new therapy has considerable promise due to its selective targeting of cancer cells and its ability to target a broad array of advanced-stage cancers.
What was the first human anti cancer vaccine? ›In 1981, the hepatitis B vaccine for liver cancer became the first FDA-approved vaccine to prevent cancer, known as a preventive or prophylactic vaccine. It is recommended that children receive the vaccine shortly after birth. Hepatitis B may increase risk of liver cancer.
What are the 3 Live vaccines? ›The live, attenuated viral vaccines currently available and routinely recommended in the United States are MMR, varicella, rotavirus, and influenza (intranasal). Other non-routinely recommended live vaccines include adenovirus vaccine (used by the military), typhoid vaccine (Ty21a), and Bacille Calmette-Guerin (BCG).
How many cancer vaccines are FDA approved? ›Preventive Cancer Vaccines
Several vaccines have been developed that can prevent HBV and HPV infection and, as a result, protect against the formation of HBV- and HPV-related cancers. Four of these preventive cancer vaccines have been approved by the U.S. Food and Drug Administration (FDA).
These prophylactic vaccines have been successful because they circumvent three major challenges facing the development of therapeutic cancer vaccines: (1) low immunogenicity; (2) established disease burden; and (3) the immunosuppressive tumor microenvironment.
How would a cancer vaccine work? ›Cancer vaccines stimulate the immune system so that it recognizes the cancer cells as foreign and attacks the cells. Cancer treatment vaccines are sometimes made with cells from the patient's own tumor, which are modified in the lab and then returned to stop, destroy or delay the growth of the cancer.
What is the disadvantage of cell based vaccine? ›The major drawback is cost. The cell based vaccines are much more expensive to produce per dose than egg based. But the benefits for development of cell based vaccines are quantifiable and visible.
How is DNA vaccine made? ›It involves the direct introduction into appropriate tissues of a plasmid containing the DNA sequence encoding the antigen(s) against which an immune response is sought, and relies on the in situ production of the target antigen.
How is an mRNA vaccine made? ›
To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies.
What is Merck's new cancer drug? ›About KEYTRUDA® (pembrolizumab) injection, 100 mg
Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings.
One FDA-approved vaccine for cancer is sipuleucel-T (Provenge®), which is used for prostate cancer that has metastasized (spread). Provenge rallies the immune system's disease-fighting forces in men who already have prostate cancer.
Can immunotherapy cure stage 4 cancer? ›Can immunotherapy cure stage 4 cancer? While immunotherapy doesn't cure stage 4 cancer, it can improve the quality and longevity of your life.
What is the number 1 cancer-fighting food? ›"Cancer-fighting foods"
The list is usually topped with berries, broccoli, tomatoes, walnuts, grapes and other vegetables, fruits and nuts. "If you look at the typical foods that reduce cancer risk, it's pretty much all plant foods that contain phytochemicals," says Wohlford.
Processed meat, overcooked foods, and fried foods may increase your risk of some types of cancer. That's because these foods may contain carcinogens, or compounds that cause cancer. Alcohol produces carcinogens when it's metabolized by your body.
What is the root cause of cancer? ›Cancer is caused by certain changes to genes, the basic physical units of inheritance. Genes are arranged in long strands of tightly packed DNA called chromosomes. Cancer is a genetic disease—that is, it is caused by changes to genes that control the way our cells function, especially how they grow and divide.
Who invented vaccine for cancer? ›Jian Zhou (Fig. 1). Sadly, Dr. Zhou, the great inventor of the vaccine, passed away in 1999 and was unable to see the benefits brought by the vaccine.
When did the cure for cancer start? ›Metastatic cancer was first cured in 1956 when methotrexate was used to treat a rare tumor called choriocarcinoma. Over the years, chemotherapy drugs (chemo) have successfully treated many people with cancer.
What is the only disease that has been eradicated? ›Widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. In 1980 WHO declared smallpox eradicated – the only infectious disease to achieve this distinction.
How the vaccines are produced? ›
Vaccines are complex biological products with lengthy manufacturing and control processes. The quality controls represent up to 70% of the full manufacturing duration. Successful manufacturing of high-quality vaccines requires international standardization of starting materials, production and quality control […]
How are HPV vaccines made? ›The HPV vaccine is made using a protein that resides on the surface of the virus. The protein is grown in the lab in yeast cells. Once the protein is grown, it assembles itself to look like the HPV virus; however, importantly, it does not contain HPV genetic material, so it can't reproduce itself or cause illness.
How was the HPV vaccine developed? ›The HPV vaccine was first developed by the University of Queensland in Australia by Professors Ian Frazer and Jian Zhou. In 1990, Frazer and Zhou began to synthesise particles that mimicked HPV, from which the vaccine would later be made.
How was vaccine invented? ›Dr Edward Jenner created the world's first successful vaccine. He found out that people infected with cowpox were immune to smallpox. In May 1796, English physician Edward Jenner expands on this discovery and inoculates 8-year-old James Phipps with matter collected from a cowpox sore on the hand of a milkmaid.
How long does it take to make a vaccine normally? ›Typical Timeline. A typical vaccine development timeline takes 5 to 10 years, and sometimes longer, to assess whether the vaccine is safe and efficacious in clinical trials, complete the regulatory approval processes, and manufacture sufficient quantity of vaccine doses for widespread distribution.
How are vaccines made using biotechnology? ›For protein-based vaccines, the coding gene of the protein can be inserted into the plasmid and transformed into the host cell (e.g. E. coli or mammalian cells) which can then can express that gene into protein. The protein produced is then harvested, purified and formulated into vaccine.
Is HPV vaccine live or killed? ›The vaccine does not contain any live virus, or even killed virus or DNA from the virus, so it cannot cause cancer or other HPV-related illnesses. When the vaccine is given, the body makes antibodies in response to the protein to clear it from the body.
Is the HPV vaccine genetically engineered? ›Protein and peptide vaccines: An organism, such as yeast, is genetically engineered to produce an HPV protein or peptide. (Small peptides also are synthesized chemically.)
Is there a lawsuit against Gardasil? ›January 18, 2023: There are now 60 active Gardasil lawsuits pending in the Gardasil class action MDL in the Western District of North Carolina. The MDL class action was established in September with just over 20 cases, which means it has already tripled.
What technology does the HPV vaccine use? ›VACCINES PREVENT HPV INFECTIONS AND ASSOCIATED DISEASES
Both Gardasil® and Cervarix® are made using recombinant DNA technology. This technology is used to generate viral proteins capable of self-assembling into so-called virus-like particles (VLPs). VLPs are made for each HPV type targeted by the vaccines.
How long was the HPV vaccine tested for? ›
More than 15 years of monitoring and research have accumulated reassuring evidence that human papillomavirus (HPV) vaccination provides safe, effective, and long-lasting protection against cancers caused by HPV infections.
What are the ingredients in HPV vaccine? ›The ingredients are proteins of HPV Types 6, 11, 16, and 18, amorphous aluminum hydroxyphosphate sulfate, yeast protein, sodium chloride, L-histidine, polysorbate 80, sodium borate, and water for injection. This leaflet is a summary of information about GARDASIL.
What is the concept of cancer vaccine? ›In recent years, researchers have developed numerous strategies to both enhance existing immune responses and trigger new immune responses to cancer. With cancer vaccination, the idea is to introduce the immune system to cancer in a way that trains it to strongly recognize the cancer as the threat that it is.