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Blood, 1 September 2001, Vol. 98, No. 5, pp. 1352-1357
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Expression of complement inhibitors CD46, CD55, and CD59 on
tumor cells does not predict clinical outcome after rituximab
treatment in follicular non-Hodgkin lymphoma
Wen-Kai Weng and
Ronald Levy
From the Division of Medical Oncology, Department of
Internal Medicine, Stanford University School of Medicine, CA.
Rituximab is a chimeric monoclonal antibody that targets
B-cell-specific antigen CD20 and an effective treatment for B-cell non-Hodgkin lymphoma. Although it is readily used in clinical practice,
the exact mechanism of its antitumor effect is unclear. One potential
mechanism involves complement-mediated cytotoxicity. It has been shown
that rituximab induces complement-mediated cytotoxicity in follicular
lymphoma cells in vitro, and complement inhibitors CD55 and CD59 may
regulate this process. To determine whether complement inhibitors play
a role in regulating the antitumor effect of rituximab, the
expression of complement inhibitors CD46, CD55, and CD59 was analyzed
in pretreatment tumor cells from 29 rituximab-treated
follicular lymphoma patients. Among them, 8 patients achieved complete
responses, 11 patients achieved partial responses, and 10 patients
showed no or minimal responses to rituximab treatment. Expression of
surface CD20, CD46, CD55, and CD59 was determined by 2-color flow
cytometry. Although the CD59 level was slightly lower in the complete
response group, there was no statistically significant difference in
the expression of individual complement inhibitor CD46 (mean channel
fluorescence [MCF]: NR, 26.4; PR, 21.9; CR, 29.9), CD55 (MCF:
NR, 16.4; PR, 14.9; CR, 23.2), or CD59 (MCF: NR, 41.6; PR, 40.6; CR,
30.6), the combination of any 2 inhibitors, or all 3 on tumor cells
from 3 response groups. In addition, there was no difference in the
rituximab-induced complement-mediated cytotoxicity in an in vitro assay
using tumor cells from 3 response groups. Thus, CD46, CD55, and CD59
expression on pretreatment tumor cells, or their susceptibility to in
vitro complement-mediated killing, does not predict clinical outcome after rituximab treatment.

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