Wednesday, October 5, 2016

More CAR-T Awesomeness

Lots of people are getting excited about the things that CAR-T treatments can do. Just when you thought it couldn't get more awesome, a new study in Cell gives us reason more reason to be excited about CAR-T for Follicular Lymphoma.

(But before I go on, I want to thank a reader named Ben for sharing his experiences with CAR-T in the comments section of a post from a few weeks ago. I didn't get a chance to respond to the comment, which is a great mix of hope for the future of this treatment, and caution about some of the side effects. Please do read Ben's comment when you get a chance.)

The article is called "Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells." Here's what it says:

So far, CAR-T cells are used as ways to help the body's immune system recognize and attack cancer cells that would otherwise get past those defenses. T cells, which usually attack invaders, are removed from the body and changed so they recognize the cancer cells as invaders. It's been a pretty effective treatment so far (again, I suggest you read Ben's comment).

But CAR-T cells can do other things, too. Because they focus in on cancer cells, they can also be used to deliver things to those cells. It's kind of like RIT, which identifies cancer cells and delivers a tiny dose of radiation. CAR-T can deliver things that don't just kill the cell, but repair it instead.

The researchers know that many cases of Follicular Lymphoma cases involve a gene called HVEM. Whn HVEM is mutated (as, of course, it is with Follicular Lymphoma), it cannot interact with a protein called BTLA. When that happens, bad things happen -- cancer cells go crazy.

(This is another of those pathway things that we're learning more about. When everything is working OK, calls behave themselves. Mess with the pathway, and all hell breaks loose. It's like a fence that keeps pigs on a path between two pens. If the fence breaks, that path gets messed up, and the next thing you know, there are pigs all over town.)

So here's where CAR-T comes in. The researchers figured out that the HVEM gene can be repaired if the HVEM protein can be delivered to the cell.  The CAR-T cells can be told to find cells that have the CD19 protein on the surface, which is a protein Follicular Lymphoma cells have. When the CAR-T cells find it, they can deliver the HVEM protein to that cell, and the cell can be repaired. No more HVEM mutation, no more messed up pathway, no more cancer. The pigs stay in the pen.

But here's what makes CAR-T so amazing.

In addition to changing T cells in CAR-T cells, researchers were also able to program the cells to keep producing the HVEM protein. T cells are meant to find an invader and then multiply and find any other similar invaders. CAR-T cells are no different, and neither are these special CAR-T cells. They will keep producing that HVEM protein, finding other cancer cells, and getting the protein to them, too. One article calls them "mini-pharmacies" -- they keep traveling around and producing the treatment that the cancer cells need. Very cool. Because the CAR-T cells are delivering a protein that only mutated cells will need, the thinking is that healthy cells will be spared, and there will be fewer side effects.

As exciting as this is, right now, it has only been tried on animal models. No humans yet. But the researchers think that their work justifies carrying on with this approach to see how well it really works.

There's definitely reason for hope with CAR-T. As relatively new as it is, we're already seeing variations of it, like this one, that seem to improve on it.

Lots to look forward to.


Anonymous said...

Great New for all of us! Keep it coming.

I always think of FL pts back in the late 90s before Rituxin. They had no idea they were on the verge of something great. I feel we are there now with novel immunotherapy options besides CAR-T, but CAR-T sounds like it has a lot of promise. But we are more in touch these days and watch the progress daily where as back then many had no idea. Yes, lots of work to be done but because the administration is done in a couple of weeks, the turn around is quick. And because people like $$$ the race is on all over the world. My onc at MDA says CAR-T will be available as a trial for FL pts in 2017 at MDA. They are using it now but for serious FL cases only (Refractory and Transformation) I probably would not jump on a trial just yet but it would be tempting to just come in for a few infusions and be done. He said they have made good progress to control the side effects also.

What strikes me most about your long term survival posts is that many pts have endured many treatments over many years. And to be honest, that's what I dread the most. But if those folks did it with the harsh treatments back then, we certainly can these days with a lot of options that not only work better, but are more tolerable. But to envision a treatment where we come in, take an infusion or 2 after having your blood "programmed" is so unbelievable. And to know that the next time you have one, it will work even better, is very reassuring.

You have mentioned the 20% sub-group a few times, along with Dr. John P. Leonard. CAR-T is certainly a game changer for them. I think folks like Ben can vouch for that. Then again...I know of a guy who took R-CHOP 17 years ago and relapsed 1 year later (a 20% guy) and has been taking just R now and then since then! We are all flakes...snow flakes that is. None of us are alike.

Fali said...

Just a quick comment Bob. When ever I feel down on the uncertainty of our future,As you know as fnl patients we are all going to be different, I read your blog. You always have something hopeful, and it cheers me up. Thanks for writing. You are like a fellow companion, with hope ,in this cancer journey.