TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL)

Summary

PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCRαβ-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. They have been transduced to express and anti-CD19 chimeric antigen receptor (CAR19) using a lentiviral vector that also incorporates CRISPR guides for genome editing of CD52 and TRAC loci in the presence of transiently provided Cas9. Recognition by TT52CAR19 T cells mediates eradication of CD19+ leukaemia and other CD19+ B cells through T cell mediated cytotoxicity. This study aims to apply PBLTT52CAR19 T cells to secure molecular remission in children with relapsed/refractory B-ALL ahead of programmed allogeneic stem cell transplantation. The cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.

Timeline

Start

2020-08-12

Primary completion

2024-03-05

Completion

2024-03-05

Outcome

Met primary endpoint

paper Other complications were within expectations, and primary safety objectives were met. PMID 36288281 ↗

Publications

• Ottaviano G, Georgiadis C, Gkazi SA, Syed F, Zhan H, Etuk A, Preece R, Chu J, Kubat A, Adams S, Veys P, Vora A, Rao K, Qasim W; TT52 CRISPR-CAR group. Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Sci Transl Med. 2022 Oct 26;14(668):eabq3010. doi: 10.1126/scitranslmed.abq3010. Epub 2022 Oct 26.

Drugs

Indications