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Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor

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dc.contributor.authorTettamanti, S.
dc.contributor.authorMarin, V.
dc.contributor.authorPizzitola, I.
dc.contributor.authorMagnani, C.
dc.contributor.authorGiordano Attianese, G.
dc.contributor.authorCribioli, E.
dc.contributor.authorMaltese, F.
dc.contributor.authorGalimberti, S.
dc.contributor.authorLopez, A.
dc.contributor.authorBiondi, A.
dc.contributor.authorBonnet, D.
dc.contributor.authorBiagi, E.
dc.date.issued2013
dc.description.abstractCurrent therapeutic regimens for acute myeloid leukaemia (AML) are still associated with high rates of relapse. Immunotherapy with T-cells genetically modified to express chimeric antigen receptors (CARs) represents an innovative approach. Here we investigated the targeting of the interleukin three receptor alpha (IL3RA; CD123) molecule, which is overexpressed on AML bulk population, CD34+ leukaemia progenitors, and leukaemia stem cells (LSC) compared to normal haematopoietic stem/progenitor cells (HSPCs), and whose overexpression is associated with poor prognosis. Cytokine-induced killer (CIK) cells were transduced with SFG-retroviral-vector encoding an anti-CD123 CAR. Transduced cells were able to strongly kill CD123+ cell lines, as well as primary AML blasts. Interestingly, secondary colony experiments demonstrated that anti-CD123.CAR preserved in vitro HSPCs, in contrast to a previously generated anti-CD33.CAR, while keeping an identical cytotoxicity profile towards AML. Furthermore, limited killing of normal monocytes and CD123-low-expressing endothelial cells was noted, thus indicating a low toxicity profile of the anti-CD123.CAR. Taken together, our results indicate that CD123-specific CARs strongly enhance anti-AML CIK functions, while sparing HSPCs and normal low-expressing antigen cells, paving the way to develop novel immunotherapy approaches for AML treatment.
dc.description.statementofresponsibilitySarah Tettamanti, Virna Marin, Irene Pizzitola, Chiara F. Magnani, Greta M. P. Giordano Attianese, Elisabetta Cribioli, Francesca Maltese, Stefania Galimberti, Angel F. Lopez, Andrea Biondi, Dominique Bonnet and Ettore Biagi
dc.identifier.citationBritish Journal of Haematology, 2013; 161(3):389-401
dc.identifier.doi10.1111/bjh.12282
dc.identifier.issn0007-1048
dc.identifier.issn1365-2141
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]
dc.identifier.urihttp://hdl.handle.net/2440/82410
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.rights© 2013 Blackwell Publishing Ltd
dc.source.urihttps://doi.org/10.1111/bjh.12282
dc.subjectAcute myeloid leukaemia (AML)
dc.subjectchimeric antigen receptor (CAR)
dc.subjectcytokine-induced killer (CIK) cells
dc.subjectIL3RA (CD123)
dc.subjectleukaemia stem cell (LSC)
dc.titleTargeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor
dc.typeJournal article
pubs.publication-statusPublished

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