Blockade of bulky lymphoma-associated CD55 expression by RNA interference overcomes resistance to complement-dependent cytotoxicity with rituximab
- PMID: 16367924
- PMCID: PMC11158893
- DOI: 10.1111/j.1349-7006.2006.00139.x
Blockade of bulky lymphoma-associated CD55 expression by RNA interference overcomes resistance to complement-dependent cytotoxicity with rituximab
Abstract
Recently, anti-CD20 (rituximab) and anti-Her2/neu (trastuzumab) antibodies have been developed and applied to the treatment of malignant lymphoma and breast cancer, respectively. However, bulky lymphoma is known to be resistant to rituximab therapy, and this needs to be overcome. Fresh lymphoma cells were collected from 30 patients with non-Hodgkin's lymphoma, the expression of CD20 and CD55 was examined by flow cytometry, and complement-dependent cytotoxicity (CDC) assays were carried out. Susceptibility to CDC with rituximab was decreased in a tumor size-dependent manner (r=-0.895, P<0.0001), but not in a CD20-dependent manner (r=-0.076, P=0.6807) using clinical samples. One complement-inhibitory protein, CD55, contributed to bulky lymphoma-related resistance to CDC with rituximab. A decrease in susceptibility to CDC with rituximab was statistically dependent on CD55 expression (r=-0.927, P<0.0001) and the relationship between tumor size and CD55 expression showed a significant positive correlation (r=0.921, P<0.0001) using clinical samples. To overcome the resistance to rituximab by high expression of CD55 in bulky lymphoma masses, small interfering RNA (siRNA) was designed from the DNA sequence corresponding to nucleic acids 1-380 of the CD55 cDNA. Introduction of this siRNA decreased CD55 expression in the breast cancer cell line SK-BR3 and in CD20-positive cells of patients with recurrent lymphoma; resistance to CDC was also inhibited. This observation gives us a novel strategy to suppress bulky disease-related resistance to monoclonal antibody treatment.
(Cancer Sci 2006; 97: 72-79).
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References
-
- Coiffier B. Immunochemotherapy: the new standard in aggressive non‐Hodgkin's lymphoma in the elderly. Semin Oncol 2003; 30 (1 Suppl. 2): 21–7. - PubMed
-
- Tan AR, Swain SM. Ongoing adjuvant trials with trastuzumab in breast cancer. Semin Oncol 2003; 30 (5 Suppl. 16): 54–64. - PubMed
-
- Hiddemann W, Dreyling M, Unterhalt M. Rituximab plus chemotherapy in follicular and mantle cell lymphomas. Semin Oncol 2003; 30 (1 Suppl. 2): 16–20. - PubMed
-
- Dillman RO. Treatment of low‐grade B‐cell lymphoma with the monoclonal antibody rituximab. Semin Oncol 2003; 30: 434–47. - PubMed
-
- Blum KA, Bartlett NL. Antibodies for the treatment of diffuse large cell lymphoma. Semin Oncol 2003; 30: 448–56. - PubMed
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