Tandem Meetings 2023 | ALL highlights: tisa-cel reinfusion in B-ALL & targeting CD5 and CD7 with CAR-Ts in T-ALL

We saw a lot of studies that confirm sort of what we already know about immunotherapy for ALL. There are increasing numbers of bispecifics, there are increasing numbers of ADCs and obviously there are many discussions about CAR T-cell products for ALL. And also in the late breaking abstracts, there was a study looking at children who had relapsed with ALL or getting second treatments with CARs, showing that that was relatively ineffective at inducing long-term remission. So that when people fail CAR therapy and have to be retreated, still we don’t exactly understand the biology sufficiently to make a huge dent in these patients. And we’re still not completely sure why these patients are not responding since many of them were still antigen-positive but didn’t respond to therapy. So it’s a little bit unclear for those patients.

Now there were some nice talks about targeting T-cell acute lymphoblastic leukemia and the problem there is that the targets you go after are also expressed on normal T-cells and so you have to get rid of those targets somehow. So there’s different ways to do it. One group from China just manufactures CAR-T until all the target population are gone. So they wait for all the cells that are negative for the target, which in this case is CD7, to get killed by fratricide. And there’s another group at St. Jude and Baylor who are focusing on a very small population of CD7-negative cells that circulate in the peripheral blood. And then there are others that are looking at not auto but Allo CAR-Ts because that makes some sense because it’s very hard to separate normal effector cells, which are T-cells, from malignant T-cell ALL cells. And so the use of off-the-shelf reagents has… there’s reasons to believe that may be a better approach. Still it’s been hard to do this.

So there was one summary by the group at Baylor who has made some significant progress targeting both CD5, which for some reason doesn’t require deleting that target or doesn’t result in significant fratricide, and CD7, which does require either deleting the target or resulting in increasing fratricide as a way of targeting T-cell ALL. And there were some interesting data presented suggesting the duration of activation before you make a CAR is very important for the CAR T-cell function, that both CD5 and CD7 are reasonable targets for T-cell ALL and for T-cell non-Hodgkin lymphoma. And so there’s some hope at least based on some proof of principle studies done by just a few groups in the world that there is hope in the future that we could potentially more efficiently target T-cell non-Hodgkin lymphomas and T-cell ALLs using CAR T-cell therapy as well.