Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro.
Monoclonal antibodies (Mabs) conjugated to toxins or their subunits (immunotoxins or ITs) are undergoing clinical testing in adults with a variety of malignancies. The potential impact of this form of therapy in pediatric precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) has yet to be determined. Mabs directed against the cell surface antigens, CD19 and CD22 conjugated to deglycosylated ricin A chain (dgRTA) have been tested in patients with non-Hodgkin's lymphoma (NHL), but not in patients with pre-B ALL. Because of the encouraging performance of these ITs in phase I trials, we evaluated the specific cytotoxicity of anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) ITs or their combination (Combotox) on patient-derived pre-B ALL cells maintained in vitro on a stromal feeder layer. After 48 h in culture, cytotoxicity to tumor cells was determined by flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated anti-CD10, 19, and 22. Both RFB4-dgRTA and HD37-dgRTA induced a statistically significant reduction in the number of viable leukemic cells, and Combotox was even more effective. Our results demonstrate that these ITs are specifically cytotoxic to primary pre-B ALL cells and that they should be further evaluated for the therapy of B-lineage ALL.
Herrera
L
L
Cancer Immunobiology Center, The University of Texas Southwestern Medical Center at Dallas, 75235-8576, USA.
Farah
R A
RA
Pellegrini
V A
VA
Aquino
D B
DB
Sandler
E S
ES
Buchanan
G R
GR
Vitetta
E S
ES
D000328:Adult; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000473:pathology; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology*; D015815:Cell Adhesion Molecules; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D037102:Lectins; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011289:Preleukemia / Q000276:immunology / Q000473:pathology*; D012276:Ricin / Q000633:toxicity*; D051918:Sialic Acid Binding Ig-like Lectin 2; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D012276:Ricin