EBMT 2025 | The potential of CAR-CIK cells for the treatment of AML

The CAR-CIK are basically T-cells which express some NK marker and are probably one of the types of cells that have been so far extensively used in immunotherapy even before the CAR-T era. 

The advantage of this cell as compared to normal T-cells is that even in the allogeneic setting, the risk of alloreactivity, which means substantially GvHD or other types of reactions related to the alloreactivity, is very minimal. So we don’t know the reason still about this peculiarity of these T-cells, which is a matter of different polarization of T-cells in order to get these cells. And that has been proven in our experience, even when we decided to move on in the CAR-T and introduce a CD19 CAR-T against a CD19 and to test it in the allo setting for relapsed/refractory acute lymphoblastic leukemia in pediatric and adult. And the result has been impressive, in the Blood Cancer Journal right now, it clearly demonstrated what has been shown in the Phase I study. 

So the advantage of these cells, which have been devoted and developed in our setting, are firstly the type of cells. Secondly, the fact that you can use the allogeneic source. And thirdly, which is probably the most important, that we use a non-viral approach. And the rate of success in terms of achieving remission, at least in the context of acute lymphoblastic leukemia relapsing after stem cell transplantation, has been very similar to what’s been obtained by commercially available CAR T-cells. 

Why in the AML context, so far, we didn’t achieve the same results as we did in the ALL or lymphoma setting? Simply because the AML context is rather more complicated. And there are many issues that, of course, are needed to be taken and considered and taken into consideration for that. Firstly, the type of antigen, because most of the antigens are basically shared with the normal stem cell. And accordingly, even in the future development, you have to think about a sort of bridge to transplant if you really want to use this type of immunotherapy approach. The second, because the microenvironment for the AML is heavily protecting the leukemia stem cell, and even worse, they are playing against the use of these cells in the immune system and immune cell in that context. For several reasons, immunosuppressive cells, another type of crosstalk between the microenvironment and the AML. 

What we are going to move on, at least in our context, is to use the same platform, which again is an allogeneic platform, CAR-CIK, for the benefit that I’d already explained, and use a sort of logic-gated dual target that is going to be, to some extent, potentially be more effective, more selective, against the target and as a second hope I have to say to be more safer in terms of target toxicity. This is already in place in the preclinical setting and all the data has been already published. And we are moving towards, because we are an academic investment, and I want to stress this point – in Europe, there are very few centers dealing with the academic effort to move on from preclinical to men in the clinical setting. And so we have already almost completed the Investigational Medicinal Product, which is of course essential. And we have already planned, jointly pediatric and adult, with the colleagues from the adult Hematology Department in Bergamo, which is a city very close by to the place where we are doing our work in the pediatric setting, which is Monza. And so we hope to open the study as a Phase I/II study by the end of this year.

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