TY - JOUR TI - Non-transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine AU - Koukoulias, Kiriakos AU - Papadopoulou, Anastasia AU - Kouimtzidis, Anastasios AU - Papayanni, Penelope-Georgia AU - Papaloizou, Andri AU - Sotiropoulos, Damianos AU - Yiangou, Minas AU - Costeas, Paul AU - Anagnostopoulos, Achilles AU - Yannaki, Evangelia AU - Kaloyannidis, Panayotis T2 - British Journal of Haematology AB - Advances in immunotherapy with T cells armed with chimeric antigen receptors (CAR-Ts), opened up new horizons for the treatment of B-cell lymphoid malignancies. However, the lack of appropriate targetable antigens on the malignant myeloid cell deprives patients with refractory acute myeloid leukaemia of effective CAR-T therapies. Although non-engineered T cells targeting multiple leukaemia-associated antigens [i.e. leukaemia-specific T cells (Leuk-STs)] represent an alternative approach, the prerequisite challenge to obtain high numbers of dendritic cells (DCs) for large-scale Leuk-ST generation, limits their clinical implementation. We explored the feasibility of generating bivalent-Leuk-STs directed against Wilms tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) from umbilical cord blood units (UCBUs) disqualified for allogeneic haematopoietic stem cell transplantation. By repurposing non-transplantable UCBUs and optimising culture conditions, we consistently produced at clinical scale, both cluster of differentiation (CD)34+ cell-derived myeloid DCs and subsequently polyclonal bivalent-Leuk-STs. Those bivalent-Leuk-STs contained CD8+ and CD4+ T cell subsets predominantly of effector memory phenotype and presented high specificity and cytotoxicity against both WT1 and PRAME. In the present study, we provide a paradigm of circular economy by repurposing unusable UCBUs and a platform for future banking of Leuk-STs, as a ‘third-party’, ‘off-the-shelf’ T-cell product for the treatment of acute leukaemias. DO - https://doi.org/10.1111/bjh.17464 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1365-2141 UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.17464 Y2 - 2021/06/02/17:31:40 KW - Wilms tumour 1 KW - acute leukaemia KW - cord blood KW - dendritic cells KW - leukaemia-specific T cells KW - preferentially expressed antigen in melanoma ER -