CAR T-cell therapy against cancer – the next generation

CAR-T therapy involves modifying immune cells (T cells) of patients in the laboratory so that they can recognize and thus target a very specific molecule on the surface of tumor cells. To minimize side effects, this molecule should occur in as few as possible other cells in the body. By contrast, it should be present in great numbers on the tumor cells, so that a strong response is triggered in the T cells against the cancer. Before now, CAR T-cells have targeted the molecule CD19, which is present on tumor cells in some forms of leukemia and lymphoma.

CD19 is not present, however, in acute myeloid leukemia (AML) cells. As an alternative target for the immune cells, there is CD33 – but this molecule is also present in many other cells of the body, making the side effects overly severe in a multi-week therapy against this molecule. To reduce negative side effects to a tolerable level while also increasing the therapeutic effect, researchers led by Professor Marion Subklewe, Medical Clinic and Polyclinic III at LMU’s University of Munich Hospital and Gene Center Munich, are modifying the system of CAR T-cell therapy such that the treatment can be quickly adapted. For example, doctors could target CD33 initially, but could then switch to other target structures on the surface of AML cells as required. The LMU researchers have developed this next-generation adapter CAR T-cell therapy in collaboration with partners in a project spanning multiple years.

“This allows us to manage and control the therapy much better than before. We can repeatedly turn it on and off again and we can design and structure treatments in a more individualized fashion. Because we can steer the CAR T-cells to several molecules on tumor cells, we expect that this will produce a stronger and broader immune response against the cancer. By replacing the adapter, we alter the tumor specificity and the approach can therefore be easily transferred to other types of cancer – including solid tumors such as bowel or lung cancer.”

D. Nixdorf, M. Sponheimer, Berghammer, D. et al.: Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML. Leukemia, 2023