Tech Blog: Department of Immunobiology Professor Creates Way to Target Autoimmune Diseases and T Lymphoma

Tuesday, November 27, 2018
Michael Kuhns, PhD, discusses the advantages of chimeric antigen receptors. Photo credit: Alison Mairena/Tech Launch Arizona

Michael Kuhns, PhD, discusses the advantages of chimeric antigen receptors. Photo credit: Alison Mairena/Tech Launch Arizona

Watch the new episode of Invented Arizona, where we speak with Michael Kuhns, PhD, about chimeric antigen receptors and targeting T lymphoma.

For this month’s blog, we had the opportunity to sit down with Michael Kuhns, PhD, associate professor in the Department of Immunobiology in the University of Arizona College of Medicine – Tucson. Kuhns, who is also a member of the BIO5 Institute, began his research journey training with 2018 Nobel Prize winner James Allison at UC Berkeley, where he studied the role of CTLA-4 in regulating CD4 T cell responses. After that, he went on to Stanford University, where his postdoctoral studies focused on the architecture and function of the TCR-CD3 complex. He came to the UA in 2010, where his research has now led to the development of a new strategy for eliminating pathogenic T cells in humans.

In pursuit of the UA’s mission of bringing the products of research to the world to improve lives, Kuhns has worked with TLA to make the invention, Targeting Pathogenic T Cell Subsets for Elimination or Reprograming Through the Use of Engineered Chimeric Receptors (5 modules CAR), available for licensing.

So, tell us a little about the background of your invention.

For any singular or multicellular organism, the fundamental process is relaying information from the outside to the inside of the cell. My lab is really concerned with the molecular machines that do that for T cells. The reason for that is T cells have to recognize antigens on a target cell to kill it, and those antigens may be from different sources, such as a bacteria or a virus or a neo-antigen in a tumor. Either way, they allow the T cell to find that problem, target the cell and kill it. What we’ve done is turn that targeting on its head. We’ve taken the molecules that the T cell may normally look at to kill a target and instead we’ve made that the receptor. That way, the T cell can be redirected to kill a T cell that would recognize that target. It sounds very complicated, but the net result would be that what we could do is target pathogenic T cells. For example, the technology we’ve developed could redirect a T cell to target those autoimmune T cells. In short, we’ve developed a series of molecules that can redirect T cells to kill pathogenic T cells.

What problem does it solve?

In addition to autoimmunity, the other thing we can do is target a T lymphoma. Once we identify whatever the target is for the T lymphoma, we can make that the receptor for our killer T cell and then use those killer T cells to target and kill the T lymphoma. Basically, we’re aiming to target and eliminate pathogenic T cells from humans. The technique can be used to target T lymphomas or autoimmune T cells, such as those associated with type 1 diabetes and multiple sclerosis, and it could potentially be used for conditioning a patient prior to transplant so that they do not get immune-mediated transplant rejection.

How is your invention different from previous solutions?

Our invention would be most akin to what people are calling chimeric antigen receptors (CAR). Typically, a current chimeric antigen receptor would be a single chain molecule that has a ligand binding region, a transmembrane domain, and a signaling motif on the inside of the cell. What we’ve done instead is to use the platform that has evolved in vertebrates over time to direct T cell function. Our chimeric antigen receptor has five modules as opposed to one module, so we call it a “5MCAR”.

Who would be the top beneficiaries of a technology like this?

This will provide the greatest benefit to people with an autoimmune disease who for whatever reason may not be responding to conventional therapies.

How will this invention change current standard practices?

This technology could be useful where other therapies fail, such as if a T lymphoma is recurring, this may be a good option, trying to target the T lymphoma in a very surgical manner. This also goes for autoimmunity. It would be a very precise way to go in and eliminate a very particular population of cells without touching the rest of the immune system. With our approach, it would be very targeted, very surgical, you could eliminate a particular population, but you wouldn’t necessarily make someone immune suppressed and then vulnerable to infection with pathogens.

Who funded the research?

This work was funded in part by my start-up funds here at the University of Arizona, in part by my RO1 grant through the NIH, and partly by The Pew Charitable Trusts.

What are you most excited about with this going forward?

My training is as a basic scientist. The work that won the Noble prize this year for check-point blockade was basic science—fundamental basic sciences—studying how the immune system works. That led to a brand new category of drugs and a brand new therapy. We’re really excited that our fundamental basic science might then lead to new developments and allow us to engineer new molecules just by studying how these molecular machines function. Based on that, we may be able to build molecular machines that can redirect the immune system to execute a particular function. That’s what we’re excited about: really fundamental basic science and then applying that knowledge to solve real-world problems.  

Learn more about this technology: 

UA14-187 Targeting Pathogenic T Cell Subsets for Elimination or Reprograming Through the Use of Engineered Chimeric Receptors

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- written by Alison Mairena
Alison Mairena
Technology Marketing Associate