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CAR-T Meeting 2022 | Exciting developments in the CAR space: novel target antigens, CAR-NKs & switchable CAR-Ts

Michael Schmitt, MD, PhD, University Clinic Heidelberg, Heidelberg, Germany, shares his thoughts on the most exciting developments in the field of chimeric antigen receptor (CAR) therapies. Whilst BCMA-directed CAR T-cell (CAR-T) therapy was originally developed for the treatment of multiple myeloma, a substantial body of evidence is indicating that BCMA could be used as a target in several non-Hodgkin lymphomas (NHL). In addition, a number of antigens such as ROR1 are currently under investigation for the development of new CAR-Ts. Moving forward, Prof. Schmitt talks on the advantages of CAR-transduced natural killer (NK) cells (CAR-NKs), which do not require tissue type matching and can be manufactured as off-the-shelf products where one healthy donor is used to make a product for a large number of patients. However, there are still a number of questions remaining in this field, notably regarding the longevity of CAR-NKs. Finally, Prof. Schmitt talks on recently developed switchable CAR-Ts, which may help reduce the side effects associated with CAR-T therapy. This interview took place at the EBMT-EHA 4th European CAR T-cell Meeting which was held virtually in 2022.

Transcript (edited for clarity)

Yeah, indeed. There is a lot of movement, motion in the field of CAR-T generation. We are very excited to see novel targets to who we can direct CARs. That is, for example, BCMA, B-cell maturation antigen. The first product has been already launched in the market for multiple myeloma patients. But we get more and more evidence that BCMA is expressed on a number of non-Hodgkin lymphomas, including chronic lymphocytic leukemia...

Yeah, indeed. There is a lot of movement, motion in the field of CAR-T generation. We are very excited to see novel targets to who we can direct CARs. That is, for example, BCMA, B-cell maturation antigen. The first product has been already launched in the market for multiple myeloma patients. But we get more and more evidence that BCMA is expressed on a number of non-Hodgkin lymphomas, including chronic lymphocytic leukemia. So this is just the tip of the iceberg. There are a number of other antigens, which are under current clinical investigation. Just to mention ROR1, which is also an interesting antigen in both leukemia and lymphoma patients. This is the first field of excitement.

And another sector of excitement comes from other cells and T-cells, which can be transected, transfused by CARs. And that is particularly natural killer cells, a lymphocyte population which does not depend on the MHC-based recognition of the HLA system. So you don’t need any longer tissue type matching. But there might be other ligands and receptors on the surface of NK cells. So NK CARs or CAR-NKs are products which can be produced from, in cases, from a single donor, a healthy donor. And then cryo-preserved and serve as an off-the-shelf cell product for a plethora of patients. So maybe from one donor, you can even make products for 100 patients. That’s just a lot of excitement. The question is how about the longevity of these natural killers? Do you need multiple transfusions of these CAR-NKs? And would that require again and again, lymphodepletion by chemotherapy, which certainly cannot be multiply administered because it brings the patient at sincere risk for infectious complications, viral, bacterial, and even funguses might develop in the patient as an opportunistic disease.

So these are fields of excitement that is added by other excitements we get from CAR-Ts which incorporate switches to switch off CAR-Ts when they have shown too rapid hemostatic expansion and put the patient at risk for cytokine release syndrome, CRS, or ICANS, immune cell-based and neuropathy syndrome.

So, a lot of things are going on and we are going to see forward what is developed in the next stage during our 4th European CAR Meeting and later on at the end of March in the EBMT Annual Meeting.

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