The health of our T cells…

[Luap001]

I am wondering if the health of T cells in CLL generally declines if there is disease progression. If it does, I would think that it might make sense to have some T cells removed and frozen for use in future CAR-T therapy. Of course there remains hope that T-cell engineering can produce a universal allogenic T-cell “inventory” - wouldn’t that be nice! But until and unless, my question remains. Wonder if anyone has any thoughts on this.

[lankisterguy Volunteer]

Hi Luap001,-

Your suggestion sounds like a great idea for research but I wonder if our CLL experts actually know enough about when our T-cells become exhausted and what causes it. Much of the current efforts around CAR-T in CLL is trying to understand this area. It seems that CAR-T works much better in other NHLs than CLL andT-cell exhaustion is the most likely suspect.

-

Len

[Justasheet1 in reply to lankisterguy]

Len,

But ibrutinib seems to be reported to restore a little of the T cell function. The other BTK’s haven’t shown that ability yet. I see that CAR-T is more successful with ibrutinib being given before hand.

Jeff

[Luap001 in reply to lankisterguy]

Perhaps the key is to evaluate those with CLL for whom CAR-T was successful versus those for whom it was not - looking for differences between the two cohorts and commonalities within each. Since CAR-T is already offered to CLL patients through clinical trials, perhaps the data already collected has the answer hidden within it; a retrospective analysis with this objective would be a perfect candidate for some researcher’s thesis or even a pharmaceutical company seeking to establish eligibility criteria for CLL patients likely to responded favorably to include in an application for regulatory approval. This could be a worthy pursuit if there are sufficient numbers of such outcomes for the analysis to be statistically meaningful. And of course the best case scenario of data that could lead to regulatory approval would also likely lead to insurance or NICE approval (as applicable) as well.

[zaax]

yes CLL patients exhibit features of T-cell exhaustion

ashpublications.org/blood/a...

[ChristineAM]

along the same line, I was wondering about collecting genetic data from those like me who have been in watch-and-wait for a long time. I've been in this category for over 13 years.

[Luap001 in reply to ChristineAM]

I agree, but such data would contribute to prognostics versus treatment. I have posted in the past a similar interest regards IGH mutations. There are literally an astronomical number of possible mutations. Still, about 40% of those sequenced have been prognostically grouped. Why not continually add to the database? Perhaps further associations with the currently identified groups as well as new groups could emerge. While only recently diagnosed, it appears I crossed the “qualifying” lymphocyte threshold about 9 years ago. While in blissful ignorance, I lived a full life and now that I am diagnosed, I continue to do so. I constantly seek to keep up both with medical developments as well as the experiences of others because perhaps one day I may be on to the next stage. Still, if or when that ever happens, my data could contribute to help future patients that may have similar disease genetics to have some information that speaks to prognostics. I know, “everyone is different”. True enough. And many doctors seem to think prognostics are not worthy of pursuit with comments like “Even if I had the data, I wouldn’t know what to do wIth it” to which I reply “Such data serves the needs of the patient without demanding anything of the attending physician.” In other words, I think most patients prefer to know where they may fit into the “collective data universe” because the probabilities can influence the ‘what and when’ of life decisions. Right now, asymptomatic and evidently nine years in, I have no sense of urgency to do anything “special”. And arguably, your life is really in the day-to-day versus the occasional vacation (that’s “holiday” for those of you in The Commonwealth). Perhaps that would change if probability indicated my experience thus far is merely the calm

before the storm. Still, for me my life is my family and the associated memories. I heard someone on television comment the other day about how he enjoyed his career but, in the end, no one from Human Resources (what was wrong with calling it Personnel?) is likely to attend your funeral. How right he is! I end with a bit of humor (humour) from an old acquaintance of many years ago, a crusty Texan, who noted: “If I do things just right, the last check I ever write will bounce.” I regret never having asked him to whom that check would have been payable if he had had the benefit of knowing it was his last. Cheers!

[newyork8 in reply to Luap001]

Made out to the IRS I would think.

[ChristineAM]

Thanks for the reply. Since I've lived outside Austin, Texas for over 20 years, I really enjoyed the quote.