Premium
Non‐transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine
Author(s) -
Koukoulias Kiriakos,
Papadopoulou Anastasia,
Kouimtzidis Anastasios,
Papayanni PenelopeGeorgia,
Papaloizou Andri,
Sotiropoulos Damianos,
Yiangou Minas,
Costeas Paul,
Anagnostopoulos Achilles,
Yannaki Evangelia,
Kaloyannidis Panayotis
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17464
Subject(s) - chimeric antigen receptor , immunotherapy , immunology , haematopoiesis , cancer research , antigen , medicine , myeloid , cd8 , cytotoxic t cell , transplantation , stem cell , biology , immune system , microbiology and biotechnology , biochemistry , in vitro
Summary 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.