Per Juliette02 's introduction, with an alternative report:
Teenager Leukaemia free after a world-first use of sophisticated cell engineering.
A 13-year-old girl who relapsed with a particular type of blood cancer is now leukaemia-free after a world-first use of what scientists have described as the most sophisticated cell engineering to date.independent.co.uk/news/scie...
- Admin
While this research, including the speed of its application, is very exciting, it is currently best applied where there are very simple DNA errors needing correcting. The cause of CLL unfortunately isn't just one DNA error, per the IGHV, FISH, TP53, ATM, NOTCH-1, etc. cytogenics reports. The increasingly rapid application of DNA editing is certainly very promising for a wide range of genetic diseases, but we need to be certain we are not causing a subsequent illness through off target editing.
Neil
Just been watching the doctor involved on the news and there are several children now involved in the trial but he did say it would be years before this could potentially be licensed, but encouraging research.
Colette
Still, big things come out of small beginnings I've seen gradual improvements in gene editing technology over the last few years. This will be the ultimate aim, curing cancer through correction of DNA damage.
All beyond my understanding but just good they are doing this research.
We want more research into our depleted immune systems. I had a great appointment last week with an immunologist who wasn’t happy with my IVIG being moved to every 8 weeks and will recommend it goes back to 4 weeks. Her senior consultant came in to speak to me and suggested that if I do get any infection to stop my prophylactic Azithromycin for my sinus and to switch to penicillin, and to always have swabs taken. So refreshing to see a new doctor who actually read all my notes, tests etc.. before seeing me 🙂
Colette
Perhaps you, Niel, or anyone else can clear a doubt I have about IG. Is IVIG better that SCIG? Does IG contain only IGg or other IGs like IGa, IGh??
As far as I understand it’s the same mix but because it’s done weekly your system is topped up frequently. I have a needle aversion and a friend of mine tried it but found it far more tiring than the infusion route.
Colette
I believe Colette is correct; the only difference is the concentration. IVIG is in a 10% concentration typically vs 20% for SCIG. IgA is typically removed to reduce the risk of an allergic reaction I think, in other illness recipoents. The quantity of other immunoglobulins also varies by manufacturer.
Neil
This might help you with your question:
It may not be a cure, but it has interesting potential. For example, what if some day you could edit out a resistance mutation?
I’ve just seen this on the bbc web site, and I understand Neil's reservations, but it’s such good news for one young girl that I’m celebrating for her 🥳🥳!
Chrisx
This research was presented yesterday as an oral poster presentation at the 2022 ASH meeting:
2001 Tvt CAR7: Phase 1 Clinical Trial of Base-Edited “Universal” CAR7 T Cells for Paediatric Relapsed/Refractory T-ALL
Background: Genome editing can overcome HLA barriers to generate ‘off-the-shelf’ CAR T cell therapies. Despite the success of CAR-T cell therapies in B-cell malignancies, the expression of shared T cell antigens has constrained the development of CAR T cells targeting T-cell malignancies, due to T cell fratricide. Targeted base editing using CRISPR guided cytidine deamination mediates highly precise C→U→T conversion which can directly disrupt gene expression without DNA breaks. This Phase I study will investigate the feasibility and safety of base edited (BE) allogeneic CAR T cells against CD7, disrupted for TCR, CD7 and CD52. The cells are used to secure remission ahead of allogeneic stem cell transplantation (allo-SCT).
Investigational medicinal product (IMP): Two allogeneic healthy donor derived BE-CAR7 T cell banks were manufactured from steady state apheresis harvests using a semi-automated process under compliant conditions. Cells were activated with an anti-CD3/CD28 reagent (Transact) and electroporated with codon optimised base editor (coBE) mRNA and three single guide RNAs targeting TRBC, CD52 and CD7. Subsequent lentiviral transduction delivered CAR7 (59-62% efficiency) and magnetic bead processing depleted residual TCRαβ+ T cells (residual 0.1-0.3%). Highly efficient disruption of CD7 and CD52 (98-99%) was confirmed by sequencing. Cells were cryopreserved and QC tested by flow cytometry, ddPCR for copy number (3.1-3.6) and replication competent lentivirus was excluded. Anti-leukemic potency was confirmed in vitro and in human:murine chimera experiments.
ash.confex.com/ash/2022/web...
My summary:
Rather than harvest a patients T-cells and then engineer them to fight their cancer, this protocol engineers donor T-cells such that they can potentially work on any patient with CD7-expressing T-cell leukemia. Basically the TRBC, CD52 & CD7 genes of the donor T-cells were disrupted by converting specific Cs to Ts in these genes by CRISPR editing allowing the CAR7 T-cells to survive and multiply (rather than attack each other in fratricide) upon infusion into the patient.
would you opine that this with CAR-NK would be a potential cure in the future?
Did you mean this question for gardening-girl ? I personally consider that CAR-NK has a better chance of curing CLL than CAR-T. NK cells seem to be more resistant to being driven into exhaustion from CLL than T cells.
It’s an open general question to all in the know. I know you are in the “know”. Thanx for answering
For those interested in a more technical article, New Scientist has reported on this development here: newscientist.com/article/23...
Qasim and his team instead used a modified form of the CRISPR gene-editing protein that doesn’t cut DNA, but instead changes one DNA letter to another, a technique known as base editing. Alyssa is the first person ever to be treated with base-edited CAR-T cells.
Re vaccine and outcome for CLL you might find this interesting
Webinar - Living with the psychological impact of leukaemia and lymphoma in the COVID-19 eraCLL INFORMATION - A developing reliable and current international list of CLL Information & Resources.Leukaemia Care Updated Patient Information - Richter's Syndrome in Chronic Lymphocytic Leukaemia 
Lab Visit
