New technology can improve immunotherapy
A new technology could take us a step closer to more successful cancer treatment by immunotherapy, shows new study.
Even though immunotherapy is one of the most promising cancer treatments available, there are still many people for who it simply does not work.
The variability in success from patient to patient has long frustrated scientists.
But a new technological method could help. It helps doctors to understand what happens when immunotherapy is successful.
The new results should help doctors to offer targeted treatments, says lecturer Sine Reker Hadrup from the Section for Immunology and Vaccinology within the National Veterinary Institute at the Technical University of Denmark (DTU).
Hadrup is one of the scientists who developed the new technology, which has been described in Nature.
Immune system needs to recognise the problems
The immunotherapy works to activate the parts of the immune system that for various reasons can be deactivated or disrupted. Especially, the immune cells known as T cells, says Hadrup.
The immune system recognises various changes in the body, including genetic changes that distinguish cancer cells from healthy cells.
But the problem is that these changes are different from person to person, says Hadrup.
“We need to understand what happens in each patient to target the immune system response to attack these specific changes. It depends on whether you have a genetic change, which your T cells can accurately identify, and this is what we can do with the new method.”
“Before we could identify 20 to 30 changes, but now we can see over 1,000. It gives us a much better overview of how the patient’s immune system reacts to immunotherapy and therefore a much greater chance of success,” she says.
Overview of T cells with the help of DNA barcodes
The T cells track the genetic changes by recognising them as foreign molecules.
To understand how T cells do this, the scientists needed to find a new method to access the T cells’ ability to recognise foreign and potentially harmful molecules.
“We did this with a new type of marker that can track which type of molecules the T cells recognise,” says Hadrup.
“We used DNA markers--small clumps of DNA that act as a barcode. We used these to read a specific bond between the T cells and the disease-related molecule. This way we can see whether the T cells are able to recognise the type of molecule that we’re interested in,” she says.
Until now, scientists and doctors used fluorescent molecules, which can be traced when they bind with another molecule. But the DNA markers can make the process more accurate and precise, which makes it easier to hit the right target, says Hadrup.
Colleague: Technical improvement, but it doesn’t change treatments yet
The T cell study won’t change treatment options just yet, says Dr. Kim Varming from the University of Aalborg, Denmark. He was not involved in the study.
It is an important technical development but it will not have any immediate impact on treatment options, he says.
“Analyses such as these have been used for some years to characterise the immune system’s reactivity, but by using DNA markers, researchers have made it possible to detect the reactivity of T cells to significantly more molecules than before,” he says.
“That’s important, research-wise, but it doesn’t directly affect the treatments available for individual cancer patients. The analysis casts light on just one aspect out of many that influence the immune system’s fight against cancer cells,” says Varming.
Important results for more than just cancer
Hadrup thinks that Varming’s reservations are unwarranted.
“I totally agree that there is still some time to go [before new treatments will emerge], but the technology certainly has a lot of potential to improve immunotherapy treatments,” says Hadrup.
“The technique can probably also improve our understanding of what role the T cells’ disease recognition plays in the development of autoimmune diseases, such as type 1 diabetes and sclerosis,” she says.
The key to effective immunotherapy
Hadrup expects to identify more molecules with the new method.
“We can probably expand the method to about 10,000 or 100,000 molecules, but the work would need to be automated. Otherwise it just takes too long. But we could do it, and in principle there’s no limit to the number of T cells we could measure,” she says.
Hadrup is optimistic about the future of T cell research.
“We all run around with around ten million different T cells, which are all different, so it’s important to learn more about each of these cells,” she says.
“We can target treatments more effectively for a range of diseases, if we know more about these connections. That is the key to effective immunotherapy.”
Translated by: Catherine Jex
- 'Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes'. doi:10.1038/nbt.3662