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Targeted therapy with MXD 3 si RNA , anti‐ CD 22 antibody and nanoparticles for precursor B ‐cell acute lymphoblastic leukaemia
Author(s) -
Satake Noriko,
Duong Connie,
Chen Cathy,
Barisone Gustavo A.,
Diaz Elva,
Tuscano Joseph,
Rocke David M.,
Nolta Jan,
Nitin Nitin
Publication year - 2014
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.13066
Subject(s) - cd22 , haematopoiesis , cytotoxic t cell , chemistry , antibody , microbiology and biotechnology , in vitro , b cell , stem cell , cancer research , biology , immunology , biochemistry
Summary Conventional chemotherapy for precursor B‐cell (preB) acute lymphoblastic leukaemia ( ALL ) has limitations that could be overcome by targeted therapy. Previously, we discovered a potential therapeutic molecular target, MDX 3 ( MAX dimerization protein 3), in preB ALL . In this study, we hypothesize that an effective si RNA therapy for preB ALL can be developed using anti CD 22 antibody (α CD 22 Ab) and nanoparticles. We composed nanocomplexes with super paramagnetic iron oxide nanoparticles ( SPIO NP s), α CD 22 Abs and MXD 3 si RNA molecules based on physical interactions between the molecules. We demonstrated that the MXD 3 si RNA ‐α CD 22 Ab‐ SPIO NP complexes entered leukaemia cells and knocked down MXD 3, leading the cells to undergo apoptosis and resulting in decreased live cell counts in the cell line Reh and in primary preB ALL samples in vitro . Furthermore, the cytotoxic effects of the MXD 3 si RNA ‐α CD 22 Ab‐ SPIO NP complexes were significantly enhanced by addition of the chemotherapy drugs vincristine or doxorubicin. We also ruled out potential cytotoxic effects of the MXD 3 si RNA ‐α CD 22 Ab‐ SPIO NP complexes on normal primary haematopoietic cells. Normal B cells were affected while CD 34‐positive haematopoietic stem cells and non‐B cells were not. These data suggest that MXD 3 si RNA ‐α CD 22 Ab‐ SPIO NP complexes have the potential to be a new targeted therapy for preB ALL .