Expansion of antileukaemia CTL lines and clones for adoptive cell therapy in paediatric patients given allogeneic haematopoietic stem cell transplantation

Recurrence of the original disease remains the main cause of treatment failure in patients given allogeneic haematopoietic stem cell transplantation for either acute or chronic leukaemia. Infusion of donor lymphocytes (DLI) is useful for rescuing patients with chronic myeloid leukaemia, while this option is of limited value in patients with acute leukaemia. Moreover, DLI may cause fatal graft-versus-host disease (GvHD) or prolonged myelosuppression. A more sophisticated approach is that of generating and expanding ex vivo T-cell lines or clones able to selectively or preferentially lyse leukaemia blasts, while sparing non neoplastic targets. In this review, we will summarize the results we have obtained in vitro utilizing an approach based on the generation of leukaemia reactive cytotoxic T-lymphocytes through the use of apoptotic leukaemia cells as source of tumor antigens. Our approach proved to be feasible and effective in the experimental model for different types of leukaemia, even when the donor was HLA-disparate with the recipient. This strategy has to be tested in the clinical setting for proving its efficacy in preventing/treating leukaemia recurrence.