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Stopping organ rejection: An end to the medication

organ transplant medicaitons

If you’re a transplant recipient you know that transplant organs are a veritable ticking time bomb waiting to be rejected by your well-meaning (but stupid) body. Not only can you do everything right and still have the organs rejected, you have to take a steady stream of expensive pills to inhibit the immune system and stop the body from launching its attack. Don’t throw your pill organizers away just yet, but soon.

First, there is no GMO hate here, and if you are afraid of genetic editing,  you may want to step away from the article as it may harm your delicate and horribly incorrect sensibilities regarding genetic editing.

Scientists have developed a gene therapy that programs a type of immune cell, called T regulatory cells (or Tregs, because that sounds much cooler) to protect transplanted tissues from rejection by the patient’s immune system.

While it is just a proof of concept at the moment, it may be the break transplant patients were hoping for.

“With further research, Tregs could be given as a living drug to prevent immune attack of transplanted cells and organs,” says Dr. Megan Levings, the study’s principal investigator.

“This exciting discovery is the first step towards testing these cells in humans undergoing transplantation.”

For those of you not familiar with transplantation, the patient’s body sometimes identifies the transplanted tissue as foreign — even though this is a very good reason to have foreign tissue — and decides to mount an immune attack against it. Because of this, while transplants are amazing and life changing, it is also a life sentence of immune-suppressing medications with very specific schedules.

From current figures in 2014, there were 2,433 solid organs transplanted in Canada and from 2010-2015, there were 52 pediatric solid organ transplants performed in British Columbia. Unfortunately, that number should be much higher, but donor organs are hard to come by because people don’t register to be a donor (hint, hint, you don’t need your organs when you are dead, I hate to break it to you).

Back to the science, “how did the researchers accomplish this feat” you may be asking. Excellent question, they took Tregs (see sounds super cool) from blood made from donations, then they built a gene that makes a protein called CAR (which sounds much more interesting when you say the whole name,chimeric antigen receptor)

Using a virus — relax it is just a vehicle, not a so-called live virus — they inserted the CAR gene into Tregs, which programmed the cells to recognize specific proteins commonly found on the surface of transplanted tissues. Normally it is the Tregs job to turn off the immune response and prevent the body from going completely crazy and attacking itself. The scientists did a series of experiments that proved the modified Tregs could recognize transplanted tissues and protect them from the immune system.

Then like good scientists, they checked to make sure that the new bad ass Tregs did what they were programmed to do. Spoiler, it worked, the Tregs did their job and kept the body from attacking the transplanted organs — which is why we are writing about it.

The idea for the modification came from a related concept that is used in a type of cancer treatment called immunotherapy where the patient’s own immune cells are genetically programmed with the CAR gene to mount an immune response against tumor cells.

“We took this approach from cancer immunotherapy and we used it for the opposite purpose – to turn off unwanted immune responses,” says Dr. Levings.

“It’s a whole new age in medicine, and we’re doing cutting edge work right here in BC,” says Dr. Katherine MacDonald, the study’s first author.

“With this finding, it opens up the possibility to build a gene for any disease where the immune system is overactive.” 

This also has implications for autoimmune diseases, which develop when the immune system destroys healthy tissues such as the insulin-producing cells of the pancreas in Type 1 diabetes or cells of the intestinal lining in inflammatory bowel disease. Basically, this is going to change a lot of things, which is good because there are a lot of people who have immune system-related problems that this could solve.

Like all big ideas, there is still a lot of research that needs to be done, about a decade of further work is needed to develop safe and targeted treatments using modified Tregs. But when it does become mainstream this won’t just be a game changer, it will be a life changer.

MacDonald, K., Hoeppli, R., Huang, Q., Gillies, J., Luciani, D., Orban, P., Broady, R., & Levings, M. (2016). Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor Journal of Clinical Investigation, 126 (4), 1413-1424 DOI: 10.1172/JCI82771

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