Article

Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models.

Genzyme Corporation, Framingham, MA 010701, USA.
Leukemia & lymphoma (impact factor: 2.4). 04/2010; 51(7):1293-304. DOI:10.3109/10428191003777963
Source: PubMed

ABSTRACT Alemtuzumab is a recombinant humanized IgG1 monoclonal antibody directed against CD52, an antigen expressed on the surface of normal and malignant B and T lymphocytes. Alemtuzumab is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), but the exact mechanism by which the antibody depletes malignant lymphocytes in vivo is not clearly defined. To address this issue, the anti-tumor activity of alemtuzumab was studied in disseminated and subcutaneous xenograft tumor models. The density of CD52 target antigen on the surface of tumor cells appeared to correlate with the anti-tumor activity of alemtuzumab. Deglycosylation of alemtuzumab resulted in a loss of cytotoxicity in vitro and was found to abolish anti-tumor activity in vivo. Individual inactivation of effector mechanisms in tumor-bearing mice indicated that the protective activity of alemtuzumab in vivo was primarily dependent on ADCC mediated by neutrophils and to a lesser extent NK cells. Increasing the number of circulating neutrophils by treatment with G-CSF enhanced the anti-tumor activity of the antibody, thus providing further evidence for the involvement of neutrophils as effector cells in the activity of alemtuzumab.

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Keywords

Alemtuzumab
 
anti-tumor activity
 
antigen
 
B-cell chronic lymphocytic leukemia
 
B-CLL
 
CD52 target antigen
 
correlate
 
effector cells
 
effector mechanisms
 
Individual inactivation
 
lesser extent NK cells
 
malignant B
 
malignant lymphocytes
 
neutrophils
 
recombinant humanized IgG1 monoclonal antibody
 
subcutaneous xenograft tumor models
 
T lymphocytes
 
tumor cells
 
tumor-bearing mice
 
vitro