CAR-T Meeting 2024 | Engineering donor-derived CAR-CIK cells towards B-ALL multi-targeting using Sleeping Beauty platform
Alex Moretti, MD, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, discusses the development of multi-targeting donor-derived CAR cytokine-induced-killer (CAR-CIK) cells using the non-viral Sleeping Beauty (SB) transposon platform, for the prevention and treatment of B-cell acute lymphoblastic leukemia (B-ALL) relapses. These CAR-CIK cells were engineered to target the CD22 and BAFF-R antigens to treat patients with CD19-negative disease following relapse. This interview took place at the EBMT-EHA 6th European CAR T-cell Meeting in Valencia, Spain.
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Transcript (edited for clarity)
I think that it’s a very fantastic moment for the research in CAR T-cells, and our group believes in non-viral CAR T-cells and in particular in the use of the Sleeping Beauty transposon platform.
The aim of our study was to develop a new strategy for facing CD19-negative relapse after CAR-T or targeted therapy against CD19...
I think that it’s a very fantastic moment for the research in CAR T-cells, and our group believes in non-viral CAR T-cells and in particular in the use of the Sleeping Beauty transposon platform.
The aim of our study was to develop a new strategy for facing CD19-negative relapse after CAR-T or targeted therapy against CD19. So we focused on two antigens, CD22 (already being tested clinically) and the BAFF receptor. First of all, we demonstrated that the two antigens were expressed upon B-ALL relapse and after a first validation of the single CAR detected against each antigen, we tried to co-electroporate the two plasmids together, and used a heterogeneous population, in which some cell expressed only the CD22 CAR, while others only the BAFF receptor CAR, and a small part the dual CAR.
We saw that this model was very good and in the preclinical model against the disease model, we demonstrated that our CAR presented a higher cytotoxicity compared to the single CAR against the CD19-positive/CD19-negative disease.
So we are happy with our result and we believe in non-viral CAR T-cells and we think that we have to try to find a new strategy to expand access to this therapy that is very exciting and innovative.
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