期刊
BLOOD
卷 112, 期 13, 页码 5180-5189出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-01-133108
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资金
- Cancer and Leukemia Group B Foundation
- D. Warren Brown Foundation
- Leukemia and Lymphoma Society
- National Cancer Institute [P01 CA101956, CA95426]
- National Science Foundation [EEC-0425626]
Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cellular cytotoxicity ( ADCC), is currently being investigated as a therapy for chronic lymphocytic leukemia (CLL). The anti-CD20 antibody rituximab is active in CLL and represents a rational agent to combine with lenalidomide. We therefore examined whether lenalidomide combined with rituximab enhances direct apoptosis and ADCC in CLL cells. In contrast to previous reports using CD20-positive lymphoma cell lines, lenalidomide down-regulated CD20 surface antigen expression in CLL patient cells via enhanced internalization, without influencing transcription. The CD20 surface antigen internalization enhanced delivery of an oligonucleotide incorporated into anti-CD20 immunoliposomes. In addition, CD20 surface antigen down-modulation by lenalidomide in CLL was accompanied by diminished rituximab-mediated apoptosis and ADCC. These observations suggest a need for alternative sequencing strategies to avoid antagonism between lenalidomide and rituximab therapy in CLL. In addition, they suggest that lenalidomide therapy might be useful to enhance targeted delivery of RNAi-based therapies using CD20 immunoliposomes in B-cell malignancies. (Blood. 2008; 112: 5180-5189)
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