Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 853-858 |
| Number of pages | 6 |
| Journal | Leukemia |
| Volume | 14 |
| Issue number | 5 |
| State | Published - 2000 |
Fingerprint
Keywords
- Childhood leukemia
- Immunotherapy
- Immunotoxins
- Monoclonal antibodies
- Pre-B ALL
ASJC Scopus subject areas
- Hematology
- Cancer Research
Cite this
Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro. / Herrera, L.; Farah, R. A.; Pellegrini, V. A.; Aquino, D. B.; Sandler, E. S.; Buchanan, G. R.; Vitetta, E. S.
In: Leukemia, Vol. 14, No. 5, 2000, p. 853-858.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro
AU - Herrera, L.
AU - Farah, R. A.
AU - Pellegrini, V. A.
AU - Aquino, D. B.
AU - Sandler, E. S.
AU - Buchanan, G. R.
AU - Vitetta, E. S.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Childhood leukemia
KW - Immunotherapy
KW - Immunotoxins
KW - Monoclonal antibodies
KW - Pre-B ALL
UR - http://www.scopus.com/inward/record.url?scp=0034090987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034090987&partnerID=8YFLogxK
M3 - Article
C2 - 10803517
AN - SCOPUS:0034090987
VL - 14
SP - 853
EP - 858
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 5
ER -