Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal antibodies for ex vivo bone marrow purging in acute myeloid leukemia.
In order to eliminate residual leukemic cells from the marrow of patients with acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the optimal conditions of utilization of three CD15 murine monoclonal antibodies (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'), whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These antibodies were also tested after fixation on magnetic beads. In a culture assay in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis of clonogenic cells greater than 99% was achieved with the three antibodies and two rounds of complement, or with antibody-coated magnetic beads. Cultures of leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with 8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh cells was low. Twenty cases were purged with antibody-coated beads. An inhibition equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with 8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than 70% and that of BFU-E higher than 95% with any method of treatment. It is concluded that efficient marrow purging of clonogenic AML cells can be achieved in some cases without toxicity for normal progenitors. The addition of other MoAbs seems necessary to obtain a significant purge in a majority of cases.
Guyotat
D
D
Département d'Hématologie, Hôpital Nord, France.
Shi
Z H
ZH
Campos
L
L
Rabat
M
M
Bonnier
S
S
Poncelet
P
P
Laurent
J C
JC
Fiere
D
D
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D003165:Complement System Proteins / Q000008:administration & dosage; D005069:Evaluation Studies as Topic; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D016256:Lewis X Antigen / Q000276:immunology*; D008863:Microspheres; D014411:Neoplastic Stem Cells / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology*; D011300:Preoperative Care; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000276:immunology; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D016256:Lewis X Antigen; D009844:Oligosaccharides; D003165:Complement System Proteins