Scientists from the Stanford University School of Medicine, US, have developed an anti-cancer vaccine based on induced pluripotent stem cells (iPSCs). The results, published in Cell Stem Cell, show that vaccinating people with their own iPS cells from many cancers can become a reality in the near future.
At present, induced pluripotent stem cells are the cornerstone of regenerative therapy. In the laboratory, many different types of cells and tissues are produced from them, capable of repairing injuries caused by trauma or disease.
In a new study in mice, scientists from the Stanford University School of Medicine suggested using iPSC training the immune system to attack or even prevent tumors.
iPS cells are capable of performing the role of a vaccine because, like many cancer cells, they resemble developmentally immature progenitor cells, which, unlike mature cells, do not have growth limitations. The researchers found that the injection of iPSCs, genetically identical to the patient, but not capable of replication, immunizes the body against cancer.
“We’ve learned that iPS cells are very similar on their surface to tumor cells”, – said Joseph Wu, MD, PhD, director of Stanford’s Cardiovascular Institute and professor of cardiovascular medicine and of radiology.
“When we immunized an animal with genetically matching iPS cells, the immune system could be primed to reject the development of tumors in the future. Pending replication in humans, our findings indicate these cells may one day serve as a true patient-specific cancer vaccine.”
“These cells, as a component of our proposed vaccine, have strong immunogenic properties that provoke a systemwide, cancer-specific immune response”, – said Nigel Kooreman, MD, and the lead author. “We believe this approach has exciting clinical potential.”
To create an iPSC, researchers obtain cell samples from an easily accessible source, such as skin and blood. Then the cells are processed by transcription factors, which cause them to “reverse” their development, turning them into pluripotent stem cells, allowing them to become nearly any tissue in the body.
In fact, iPSCs are similar in their properties to embryonic stem cells. One of the key criteria of pluripotency is the ability of the cells to form a tumor called a teratoma, which is composed of many different cell types, after the cells are injected into animals (iPSCs used in regenerative-medicine therapy are grown in the presence of special proteins that guide their development to the path of final specialization into specific cell populations before being used clinically).
It is known that cancerous and immature cells also have many similar characteristics. So, for example, in process of oncotransformation, cells often shed the naturally occurring mechanisms that serve to block inappropriate cell division and instead begin proliferating rapidly.
Wu and Kooreman decided to find out how similar the iPSCs and cancer cells are to each other. They compared the gene expression panels of the two cell types in mice and humans and found some remarkable similarities surface proteins that can serve as targets (epitopes) for the immune system.
To confirm their hypothesis, scientists used four groups of mice. The first (control) was injected with control solution, the second – genetically matching (autologic) iPSC, that had been irradiated to prevent the formation of teratomas, the third group received an adjuvant – immune-stimulating agent, and the fourth group – a combination of irradiated iPSC and adjuvant.
All animals in each group were injected once a week for a month. Lastly to monitor the potential growth of tumors, into all experimental mice were transplanted with the breast cancer cell line.
A week after transplantation, all mice were found to have developed tumors of the breast cancer cells at the injection site.
Although the tumors grew robustly in the control groups, they shrank in size in 7 out of 10 mice vaccinated with iPS cells plus the adjuvant. Two of these mice were able to completely reject the breast cancer cells and live for more than one year after tumor transplantation.
Similar results were obtained after Kooreman and his colleagues transplanted the cell line of murine melanoma and mesothelioma (a type of lung cancer) into mice.
Scientists also found that T-cells of vaccinated mice are able to slow the growth of breast cancer cells in unvaccinated animals. Conversely, these T cells also blocked the growth of teratomas in mice injected with non-irradiated IPS. This shows that activated T cells equally recognize the epitopes of iPS and cancer cells.
“This approach is particularly powerful because it allows us to expose the immune system to many different cancer-specific epitopes simultaneously”, – Kooreman said.
In the future, researchers would like to study whether this method will work in the laboratory with cancer samples and human immune cells. Scientists believe that, if successful, it is possible to create a vaccine based on their own irradiated iPSCs as a way to prevent the development of cancer for several months and even years.
Alternatively, the iPS cells could potentially be used as a part of the standard of adjuvant care after primary surgery; chemotherapy or radiation therapy, or both; or immunotherapy as a way to treat established cancers.
“Although much research remains to be done, the concept itself is pretty simple”, – Wu said. “We would take your blood, make iPS cells and then inject the cells to prevent future cancers. I’m very excited about the future possibilities.”