In:
British Journal of Haematology, Wiley, Vol. 161, No. 3 ( 2013-05), p. 389-401
Abstract:
Current 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 ( CAR s) represents an innovative approach. Here we investigated the targeting of the interleukin three receptor alpha ( IL 3 RA ; CD 123) molecule, which is overexpressed on AML bulk population, CD 34 + leukaemia progenitors, and leukaemia stem cells ( LSC ) compared to normal haematopoietic stem/progenitor cells ( HSPC s), and whose overexpression is associated with poor prognosis. Cytokine‐induced killer ( CIK ) cells were transduced with SFG ‐retroviral‐vector encoding an anti‐ CD 123 CAR . Transduced cells were able to strongly kill CD 123 + cell lines, as well as primary AML blasts. Interestingly, secondary colony experiments demonstrated that anti‐ CD 123. CAR preserved in vitro HSPC s , in contrast to a previously generated anti‐ CD 33. CAR , while keeping an identical cytotoxicity profile towards AML . Furthermore, limited killing of normal monocytes and CD 123‐low‐expressing endothelial cells was noted, thus indicating a low toxicity profile of the anti‐ CD 123. CAR . Taken together, our results indicate that CD 123‐specific CAR s strongly enhance anti‐ AML CIK functions, while sparing HSPC s and normal low‐expressing antigen cells, paving the way to develop novel immunotherapy approaches for AML treatment.
Type of Medium:
Online Resource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2013.161.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
80077-6
detail.hit.zdb_id:
1475751-5