Cancer Cell Carbohydrates Help Create an Innovative Vaccine
Denmark-based researchers announced on January 26, 2022, that chemists are copying cancer cell carbohydrates in the laboratory for inclusion in a vaccine that activates the immune system.
The surface of all cells is covered with different carbohydrates.
On cancer cells, however, the carbohydrates often differ from the carbohydrates located on the surface of healthy cells.
In a press release, Professor Mads Hartvig Clausen and Postdoc Cecilia Romanò from Technical University of Denmark (DTU) Chemistry stated they are trying to 'exploit this difference to develop a cancer vaccine.'
"With such a vaccine, it will be possible to teach our immune system to recognize the difference between a healthy cell and a cancer cell so that the cancer cells are attacked and destroyed by the immune cells," says Mads Hartvig Clausen.
The vaccine is based on imitations of the surface carbohydrates of cancer cells—which are called tumor-associated carbohydrate antigens (TACA)—and which DTU chemists can produce artificially in the laboratory using chemical synthesis.
"The carbohydrates are only found in small quantities on the surface of cancer cells, but we can produce large quantities in the laboratory."
"When the vaccine is injected under the skin, the immune system will be presented with our copies of the TACAs."
"They are to act as antigens, which means that they must activate the immune system to produce antibodies."
"The idea is that if a person's immune system subsequently encounters these carbohydrates because he or she has developed cancer, it will be able to recognize them and consequently combat the cancer cells," says Mads Hartvig Clausen.
This concept sounds surprisingly simple.
Yet the chemists had already faced several challenges that needed to be addressed before they were ready with an initial cancer vaccine candidate. And the chemists were aware that they required close collaboration with other disciplines at DTU if they were to succeed with their ambition.
"When we started, we knew the strong competencies that exist at DTU in immunology and drug delivery."
"We're experts in chemical synthesis, but we need to collaborate on the other aspects if we're to succeed in developing the vaccine, and we, therefore, got together with colleagues from DTU Health Tech and DTU Bioengineering," explains Mads Hartvig Clausen.
The first challenge for Mads Hartvig Clausen and Cecilia Romanò was to select the types of TACAs to be produced in the laboratory.
Because—with cancer—there is not just one kind of carbohydrate on the surface of all cancer cells. The TACAs vary from cancer type to cancer type, just as each cancer type has several kinds of TACAs on the surface of the cells.
At DTU, the choice fell on a group of carbohydrates associated with malignant melanoma cancer, neuroblastoma (a type of tumor in the body of children), and small cell lung cancer.
"With such a vaccine, it will be possible to teach our immune system to recognize the difference between a healthy cell and a cancer cell, so that the cancer cells are attacked and destroyed by the immune cells."
"These are primarily three cancers that have the same type of carbohydrate on their cell surface, namely the carbohydrates known as gangliosides. Therefore, they can be produced in the laboratory from simple sugars that we can buy for this purpose," says Cecilia Romanò.
The next challenge was to ensure that the carbohydrate activates an immune response in the body when injected.
According to the two chemists, there is an obstruction, as the body is 'a friend of carbohydrates'—meaning that carbohydrates are generally not very strong antigens.
"Carbohydrates generally don't activate a robust response from our immune system."
"Therefore, we had to find a way to help our artificial carbohydrates elicit the desired immune response," says Cecilia Romanò.
Amplifying the effect of a pharmaceutical is a well-known challenge, and the solution may be to use an excipient—an adjuvant.
Mads Hartvig Clausen and Cecilia Romanò chose to use the excipient α-galactosylceramide as an adjuvant.
This substance consists of carbohydrates and fatty acids—a so-called glycolipid—which stimulates the immune system. To boost the immune response further, the chemists compounded the antigen and the adjuvant in the laboratory.
This means that they 'coupled' their selected TACA with α-galactosylceramide, so they became one compound instead of two' loose substances.'
"We've subsequently demonstrated that it gives a stronger immune response when the two substances are joined than if they are given individually," explains Mads Hartvig Clausen.
Assimilation in the body is ensured.
Before the chemists could inject their antigens, they were aware that something was needed to help the substances be assimilated into the immune system.
"We needed a kind of carrier to ensure that the immune system can detect and respond to our antigens. Otherwise, we will not be able to start the cascade of events which makes up an immune response and which results in the actual production of antibodies," explains Mads Hartvig Clausen, who approached his colleagues at DTU Health Tech, Associate Professor Jonas Henriksen and Professor Thomas Andresen.
They have been collaborating for many years. As a result, the chemists were familiar with their colleagues' work with liposomes (a fat globule the size of a nanoparticle) used for drug delivery and vaccine formulation.
Mads Hartvig Clausen and Cecilia Romanò were thus able to have their cancer antigens 'mounted' on a liposome, which was well described and documented assimilation by the immune system.
The chemists could now start testing their vaccine. So far, they have performed one trial with mice.
They were all cancer-free because the researchers were initially interested in finding out whether their vaccine would create the desired immune response at all.
The results were really good, say Mads Hartvig Clausen and Cecilia Romanò.
"We've shown that our vaccine triggered the immune system of the mice into producing antibodies that can recognize cancer cells with our selected carbohydrate on the surface. The antibodies can also communicate that components from the immune system—the so-called complement system—can kill cancer cells in the laboratory," said the two chemists.
The researchers will optimize the vaccine in the next two to three years and further understand the immune response.
The next step will be testing on mice with cancer to see if the antibodies produced by the vaccine will fight the disease.
In parallel, the researchers applied and received funding for starting processes with a consultant that will pave the way for getting the vaccine out of the laboratory and onto a commercial market.
"If society is to benefit from our vaccine one day, we will need a company to take over our invention so that it can be tested in humans and then—hopefully—be put into production," says Mads Hartvig Clausen.
The researchers hope to hand over their cancer vaccine candidate to a pharmaceutical company in about three years.
Note: DTU is an independent and self-governing university with a Board of Governors. Hans Christian Ørsted founded DTU in 1829 with a clear vision to develop and create value using science and engineering to benefit society.