Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia

Mené sur 3 enfants atteints d'une leucémie lymphoblastique aiguë à cellules T récidivante, cet essai de phase I évalue la faisabilité d'une immunothérapie à base de lymphocytes CAR-T ciblant l'antigène CD7

Résumé en anglais

Background: Cytidine deamination that is guided by clustered regularly interspaced short palindromic repeats (CRISPR) can mediate a highly precise conversion of one nucleotide into another — specifically, cytosine to thymine — without generating breaks in DNA. Thus, genes can be base-edited and rendered inactive without inducing translocations and other chromosomal aberrations. The use of this technique in patients with relapsed childhood T-cell leukemia is being investigated.

Methods: We used base editing to generate universal, off-the-shelf chimeric antigen receptor (CAR) T cells. Healthy volunteer donor T cells were transduced with the use of a lentivirus to express a CAR with specificity for CD7 (CAR7), a protein that is expressed in T-cell acute lymphoblastic leukemia (ALL). We then used base editing to inactivate three genes encoding CD52 and CD7 receptors and the