CAR-T cell therapy is in the news once again, with announcements this morning that a second baby's life has been saved using this revolutionary new treatment; I previously blogged about the first success at Great Ormond Street Hospital (GOSH) towards the end of last year, where a first young life was saved after all other options had run out.
That baby (Layla) was around the 1-year-old mark which is positively mature in comparison to the child in the second case who was diagnosed with the possibly fatal, advanced leukemia a mere four weeks after birth. The groundbreaking UCART19 therapy was applied to this second baby on compassionate use grounds, and like the previous case, this baby is now in remission. Incredible but true!
This is spectacular progress even if it goes without saying that it still only represents n=2, but I bet you that the parents of those two babies aren't worrying very much about such statistics right now! Ditto the two babies who may now get to grow into children and then into young adulthood and beyond, all being well.
Cellectis are hardly alone in this brave new world of cell therapy, and are racing ahead alongside competitors such as Novartis, Juno and Kite, but Cellectis do stand out for one very specific and not insignificant reason. While the former three are championing the use of "autologous" T-cell therapy, Cellectis are utilizing a variation on that theme referred to as "allogeneic" therapy.
The bottom line of that difference is that while the others are using the patient themselves as the donor, and are modifying patient-derived cells for subsequent reintroduction, in the case of UCART19 the modified T-cells are derived from a healthy matched donor. That donor's T-cells are altered in three fashions to achieve what would have been impossible even a few years ago: firstly, they are designed to be resistant to a biologic being used on the patient; secondly, they are altered so as to not attack the healthy tissue of the recipient; and lastly, they are equipped with potent cancer-targeting and killing potential.
That's a pretty nifty combination of properties when they get it right, as they clearly did in the case of these two children. Of course, this approach needs some rigorous clinical testing before regulatory approval, and Cellectis are slated to begin such trials later in the year, in collaboration with both Pfizer and Servier. Cellectis CEO Dr. André Choulika elaborated on the strategy in an interview with CNBC that was aired this morning, and one interesting aspect of the discussion was Choulika's assertion that when you use a patient's own cells, it is a procedure, not a product!
Although the occasionally rambling interviewer got in the way of the subject matter a little, he actually did seem to have a grasp of the potential problems using this type of technology, and I think a layman audience probably benefited from his gruff and somewhat rambling questioning style. Choulika held firm to the beauties of his company's technology, which is in principle a much more "off the shelf" and less expensive version of autologous cell therapy offered by his competitors.
I am extremely interested in where this is all going, not least because it involves not only one but two key advances in modern molecular medicine, and that is the combination of gene editing and T-cell immunotherapy. The Cellectis technology uses a gene-editing tool known as "TALEN" to edit the T-cell repertoire in healthy donor cells to favourably alter their properties, and then introduces them into the recipient to invoke T-cell-mediated tumour cell death. Separately, such techniques are still considered largely avant garde, and the combination of them clinically in UCART19 is positively futuristic in nature.
We are keeping a very close eye on such developments at AmorChem, because we have two related programs in our portfolio - one which utilises a modification of the TALEN tool used in these children's treatment, and the other which is a high-profile allogeneic immunotherapy approach also utilising donor T-cells to attack patient cancer cells, in this case via a single mismatched minor histocompatibility antigen. The results obtained at GOSH and in the CAR-T field in general are very encouraging indeed, and imply that the days of human gene editing in disease as well as using modified T-cells to eliminate cancers are both just around the drug development corner!
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