alloCART-LMA

Artículos científicos

• “Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia” Calviño C, Ceballos C, Alfonso A, Jauregui P, Calleja-Cervantes ME, San Martin-Uriz P, Rodriguez-Marquez P, Martin-Mallo A, Iglesias E, Abizanda G, Rodriguez-Diaz S, Martinez-Turrillas R, Illarramendi J, Viguria MC, Redondo M, Rifon J, Villar S, Lasarte JJ, Inoges S, Lopez-Diaz de Cerio A, Hernaez M, Prosper F, Rodriguez-Madoz JR.Front Immunol. 2023 Sep 19;14:1270843. doi: 10.3389/fimmu.2023.1270843. eCollection 2023. PMID: 37795087
• “CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome”
  Rodriguez-Marquez P, Calleja-Cervantes ME, Serrano G, Oliver-Caldes A, Palacios-Berraquero ML, Martin-Mallo A, Calviño C, Español-Rego M, Ceballos C, Lozano T, San Martin-Uriz P, Vilas-Zornoza A, Rodriguez-Diaz S, Martinez-Turrillas R, Jauregui P, Alignani D, Viguria MC, Redondo M, Pascal M, Martin-Antonio B, Juan M, Urbano-Ispizua A, Rodriguez-Otero P, Alfonso-Pierola A, Paiva B, Lasarte JJ, Inoges S, Lopez-Diaz de Cerio A, San-Miguel J, Fernandez de Larrea C, Hernaez M, Rodriguez-Madoz JR, Prosper F.Sci Adv. 2022 Sep 30;8(39):eabo0514. doi: 10.1126/sciadv.abo0514. Epub 2022 Sep 30. PMID: 36179026

The primary goal of the alloCART-LMA project is to develop and evaluate innovative therapy strategies based on using genetically modified immune cells for treating acute myeloid leukaemia (AML). Specifically, it is based on developing CAR T cells, which are genetically modified T lymphocytes to express a chimeric receptor that makes it possible to recognise and eliminate tumour cells. CAR T therapies are generally used in an autologous context, which means cells from the same patient are used for modification, and they are re-introduced into the patient and the tumour is thus eliminated. That therapy has been very effective with some diseases, like acute lymphocytic leukaemia or lymphoma.

However, in some cases, using CAR T therapies in patients with AML has serious limitations. In some cases, the T cells of those patients are not valid for generating CAR T cells. And, furthermore, in many cases patients with AML have very severe relapses that prevent current CAR T therapies from arriving in time. Because of all that, developing new therapies that make it possible to treat those patients is necessary.

To those ends, a very interesting approach is using healthy donated CAR T cells (allogenic therapy, thus the name alloCART-LMA), which will let us have a therapeutic product ready to use whenever it is needed. However, using cells from a donor in a patient has limitations, because the patient’s immune system would reject the CAR T cells (because they are from a different person) and, furthermore, CAR T cells could react with the patient (because they are from a different person).

In order to solve that problem, the alloCART-LMA project proposes using gene editing technologies to eliminate the key molecules responsible for the adverse affects from the CAR T cells. Thus, with T cells from a healthy donor, we can create genetically modified CAR T cells that can be used universally.

During the alloCART-LMA project we fine-tuned the creation of those cells, and we evaluated their functionality and capacity to recognise and eliminate tumour cells in the laboratory, like in animal models with rats that have the disease. The results of this project were highly satisfactory, because we fine-tuned a very efficient production protocol, and the CAR T cells created are completely functional. That makes it possible for us to go further with developing this model and work on producing the cells at a large scale and under manufacturing standards compatible with clinical use. The following steps will lead us to being able to evaluate the cells in clinical trials, and get closer and closer to being able to provide a new therapy for patients with AML