Gene-edited healthy donor CAR T cells show superior anti-tumour activity compared to CAR T cells derived from patients with lymphoma in an in vivo model of high-grade lymphoma
Charlotte Graham, Agnieszka Jóźwik, Ruby Quartey‐Papafio, Nikolaos Ioannou, Ana M. Metelo, Carlo Scala, Glenda J. Dickson, Orla Stewart, Maria Almena-Carrasco, Elisa Peranzoni, Alan G. Ramsay, Piers Patten, Thomas Pertel, Farzin Farzaneh, Sandra Dupouy, Andrea Pepper, Reuben Benjamin
Abstract
CD19-targeted autologous chimeric antigen receptor (CAR) T-cell therapy has shown dramatic response rates in relapsed and refractory patients with B-cell malignancies However, a growing body of literature has demonstrated T-cell dysfunction in some cancer patients, which impairs the effectiveness of the end CAR T-cell product Healthy donor (HD) CAR T cells could potentially provide a source of more functional cells. Graft-versushost disease (GvHD) limits the use of non-HLA-matched HD CAR T cells, but gene-editing to remove the native alpha beta T-cell receptor (TCR) from HD CAR T cells has allowed HD TCR -CAR T cells to be given to HLA unmatched patients with B-acute lymphoblastic leukaemia or with B-cell lymphoma in clinical trials