| Title |
Non-transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine |
| ID_Doc |
16152 |
| Authors |
Koukoulias, K; Papadopoulou, A; Kouimtzidis, A; Papayanni, PG; Papaloizou, A; Sotiropoulos, D; Yiangou, M; Costeas, P; Anagnostopoulos, A; Yannaki, E; Kaloyannidis, P |
| Title |
Non-transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine |
| Year |
2021 |
| Published |
British Journal Of Haematology, 194, 1 |
| DOI |
10.1111/bjh.17464 |
| Abstract |
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. |
| Author Keywords |
acute leukaemia; cord blood; dendritic cells; Wilms tumour 1; preferentially expressed antigen in melanoma; leukaemia‐ specific T cells |
| Index Keywords |
Index Keywords |
| Document Type |
Other |
| Open Access |
Open Access |
| Source |
Science Citation Index Expanded (SCI-EXPANDED) |
| EID |
WOS:000654097500001 |
| WoS Category |
Hematology |
| Research Area |
Hematology |
| PDF |
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.17464
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