Gemtuzumab ozogamicin (Mylotarg) has therapeutic activity against CD33 acute lymphoblastic leukaemias in vitro and in vivo.
Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. As approximately 18% of acute lymphoblastic leukaemias (ALL) are also CD33 positive, we have investigated the cytotoxic activity of GO on CD33+ ALL cells in vitro and in vivo. 10 ng/ml GO induced 30-95% inhibition of thymidine uptake and 30-70% cell death in four freshly isolated and one in vivo passaged CD33+ ALL-cell cultures. Furthermore, an in vivo model of a CD33+ ALL carrying the Philadelphia chromosome [t(9;22)] was established. 5 x 10(6) ALL-2 cells inoculated in the tail vein of severe combined immunodeficient mice engrafted into haematopoietic organs, reaching a mean of 70%, 61% and 69% human CD45+ cells in bone marrow, spleen and liver, respectively, at 35 d. To test the therapeutic activity of GO, 50 or 100 microg immunotoxin was inoculated i.p. on days 7, 11 and 15 following tumour-cell inoculation. GO treatment dramatically inhibited expansion of ALL-2 cells in all tested organs and increased survival of tumour-injected animals by 28-41 d, relative to controls. These data demonstrated that GO is active both in vitro and in vivo against CD33+ ALL cells.
Golay
J
J
Laboratory of Cellular and Gene Therapy 'G. Lanzani', Division of Haematology, Ospedali Riuniti di Bergamo, Bergamo, Italy. jgolay@isoedakuruyniti.bergamo.it
Di Gaetano
N
N
Amico
D
D
Cittera
E
E
Barbui
A M
AM
Giavazzi
R
R
Biondi
A
A
Rambaldi
A
A
Introna
M
M
D000617:Aminoglycosides / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D016923:Cell Death / Q000187:drug effects; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D016130:Immunophenotyping; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D063268:Sialic Acid Binding Ig-like Lectin 3; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D000922:Immunotoxins; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab