T-cells are the cells responsible for fighting off foreign cells. Without them, humans are vulnerable to disease. The T-cells don’t act alone, however. They rely on immune system sentinels called dendritic cells. These helper cells seek our tissues for foreign particles, such as bacteria, viruses or cancer cells, to devour them. When they do, it breaks down the particles into smaller pieces, known as antigens. These particles are then presented on the surface to the immune system’s killer cells (T-cells).
This process is manipulated to get our own bodies to attack cancerous cells in cancer treatments like immunotherapy. Recently, a research team from Lund University in Sweden has developed a process that takes this manipulation one step further. They have found a way to convert human skin cells into these immune system sentinels, which could lead to safer immunotherapy treatment options.
“We are merging two different areas of research. One of them is reprogramming stem cells and the other is immunology. We can use it to make advances in immunology and cancer immunotherapy.” – Pereira
The thing about immunotherapy is that fighting cancer with the body’s own immune system is no easy task. This is because sometimes cancer may cause the dendritic cells to behave in unusual ways. When that happens they do not function properly. Other times, the body might reject the treatment altogether.
However, they have found that by creating immune cells from a patient’s own body the chance of rejection is drastically reduced. They have termed this new process “direct reprogramming”. The research is published in the journal Science Immunology. Their findings open up the possibility of developing novel dendritic cell-based immunotherapies against cancer.
“Our study has shown that reprogrammed cells have the ability to effectively capture and present antigens to killer cells in the same way as ‘natural’ dendritic cells.” – Filipe Pereira
Direct reprogramming has been proven to be fast and effective. These reprogrammed cells are able to alert the body’s immune system to cancerous cells and they can also be guided by researchers to seek out specific targets before they are introduced into the body. Filipe Pereira, the leader of the research team that conducted the study said:
“From a tissue section taken from the skin, we can cultivate millions of cells and reprogram them to dendritic cells in a process that takes only nine days.”
Furthermore, this finding opens up future possibilities to develop new strategies for immunotherapy against solid tumors and blood cancers, beyond the treatments currently available. Pereira explains:
“Tumors often undergo a number of mutations, developing into a heterogeneous entity, which makes it more difficult for the immune system to identify them as a threat. In a more creative perspective, we now want to explore the process of dendritic cell reprogramming to develop a cancer gene therapy. We are aiming at injecting the three reprogramming proteins straight into the tumor forcing it to present their own tumor-specific antigens. This allows the activation of the killer cells against tumour cells and may lead to their elimination. We have named this concept TrojanDC in an analogy with Homero’s Trojan horse. The great potential of this technology for cancer treatment lead us to start a new company together with Lund University for the development of this concept into a product that hopefully will reach cancer patients one day.”
Cellular immunotherapy itself, apart from reprogramming cells, is yet a relatively new treatment option for fighting cancer. Which means there is much potential down this path of treatment with brilliant ideas such as this manifesting. Pereira has formed a company to explore the clinical potential of the technology called Asgard Therapeutics. Pereira concludes:
“Additionally, our studies open up the possibility of reprogramming other dendritic cell sub-types taking advantage of their distinct functional features. A better understanding of the mechanisms that determine the identity of immune sentinels and of how to use this knowledge to reprogram other cell types into dendritic cells could make these patient-specific cells useful in the clinic.”
With researchers working so diligent to better understanding the intricacies of how our immune systems function we will be able to stay healthy for longer. Thanks To the research conducted by Pereira and his team, direct reprogramming will help to improve treatment options and open new avenues of immunotherapy research in the years to come.