CAR T PROGRESS

[wizzard166]

Many of us have interest in and hopes for a new treatment that can be a breakthrough with our illness. As such there has been a good bit written on our site about the hope of CAR T treatment. CAR T has shown incredible success with many cancers so far, but it has had its problems with our illness. The reason is the therapy counts on healthy T Cells taken from the patient's body, then modified genetically to seek out the cancer cells they can destroy. Then the modified T Cells are multiplied in a growth medium and then infused back into the patients own body. The T Cells of CLL patients are known to already be very reduced in ability, before they are taken from our bodies. So the chances for CAR T therapy to work in us is very limited. There was that one case in Philadelphia we all have read about that defied this problem, but mainly only that one case.

Dana Farber (where I'm followed) along with NYU just finished a study on why our CAR T cells reach Exhaustion from our illnesses, and what can be done to reverse or prevent that exhaustion. They believe based on initial studies in animals that they have found the answer, and believe a process of genetic engineering can change our T Cells to avoid the exhaustion.

After reading this article today, I felt it was worthwhile sharing with our group. I realize it will have language that is beyond many of our group, but then there are many in our group who are very capable of reading and understanding it. Even those of you who don't have the biology background to understand a lot of it should still give it a read. I believe that you will still understand the hope that this now gives to all of us, even if you don't understand the process they hope to use to succeed.

Here is the link to the article dana-farber.org/newsroom/ne...

Carl

[AussieNeil Partner Administrator]

Actually 2 of the original CLL patients survived 10 years, only for one to die from complications stemming from COVID-19, which is very sad to learn. These brave volunteers had exhausted other available treatment options. Not much has changed in that regard - yet! From The American Journal of Managed Care®

"The 2 patients in the study received their CLL diagnosis in 1996 and 2000. A statement from the University of Pennsylvania said that one of the patients lived until early 2021, when he died of complications stemming from COVID-19.

The other patient, Doug Olson, 75, is healthy and in interviews this week said he was cured. In 2018, The American Journal of Managed Care® interviewed Olson ajmc.com/view/looking-back-... after he participated in a Medicare Evidence Development and Coverage Advisory Committee meeting about the use of patient-reported outcomes in coverage decisions for CAR T therapy."

ajmc.com/view/car-t-cells-p...

Neil

[LeoPa in reply to AussieNeil]

Does he have any B cells left? Did the car t kill only the monoclonal ones?

[AussieNeil Partner Administrator in reply to LeoPa]

I don't know of any CLL treatments that have been proven to selectively target CLL cells, leaving maturing/similar stage B cells alone. Venetoclax and the BTKi drugs can hit CLL cells a bit harder, because they tend to over-express the targets.

[The-Man-with-a-Plan]

Wizzard

Thanks for sharing this link. I have a very strong interest in the concept of T-Cell Exhaustion and CLL. When I shared my concern about T-Cell Exhaustion with my CLL specialist a year ago, he was a bit dismissive of the concept. He is one of the top CLL docs in the country so I was surprised by his response. Anyway, after reading the study summary and findings, I now have some additional information to share with him.

The Man

[Greenbunnies]

I watched a webinar with Prof George Follows at the weekend, organised by the CLL Support Association. He briefly discussed the difficulties of CAR-T in CLL, and his overall take on the prospects for this treatment was quite negative. Although he thinks it is viable for some types of lymphoma, it's unlikely to be further developed for CLL because the costs/complexities are too high and the CLL 'market' not big enough. Quite gloomy and I hope he was wrong!!

Having said that, he was extremely positive about further development of current treatment approaches (BTKi, BLC2i etc) - there is obviously a lot more innovation in the pipeline and hopefully future treatments that we can all benefit from.

One approach I'm fascinated by is this recent Stanford announcement about a completely novel approach where leukaemia cells are reprogrammed to train T-cells to recognise multiple antigens:

med.stanford.edu/news/all-n...

[wizzard166]

Hey Mann

I was a Biology major in college who had hopes one day of being a physician; however, I ne ver made it to Medical School. That was fifty four years ago that I graduated, so its not too easy for me to follow medical articles that well. Still I have enough ability to read and sort of understand what they are talking about, and this article gave me a lot of reason to be confident that they will remedy the exhaustion syndrome with our T Cells. My Brother who is one of those super brilliant MD types whose knowledge and mental functioning is in outer space once told me: "if ever there is a cure for CLL it will be genetic" What the article I posted is saying is that they can genetically modify the exhausted T Cells to regain functioning, and them in culture environments have them grow in numbers into the millions. Then send this army of millions back into our bodies, and have the Killer T Cells literally seek out the non functional cancerous lymphocytes that we have and destroy them. Then once they eradicate the cancer cells, they will take up Watch in our bloodstream and immediately kill any new ones.

That of course is only one type of genetic approach, and thank goodness for it. The true cure will be to genetically modify the mutated White Blood Cells we have to be normal again. I see that happening too in the future; just don't know, if at my age I'll ever get to see it. I do believe at my age I'll get to see the CAR T approach working with CLL

Carl

[acanfill]

Just curious,

Has there ever been any thought on harvesting a person's T-cells when they're initially diagnosed with CLL? So in the future if CAR-T is an option the t-cells may not be as badly damaged from disease progression and previous treatments. Just a thought....does this seem like a viable option?

Andrew

[wizzard166 in reply to acanfill]

Andrew I'm not sure if they ever looked at that idea; however, I think the immune system is pretty damaged already at the time of diagnosis.

[bennevisplace]

Thanks Wizard, this is a find and a half!

The Dana Farber article doesn't include a web link to the paper in Molecular Cell. Here it is sciencedirect.com/science/a...

also downloadable as .pdf