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Blood, 15 July 2006, Vol. 108, No. 2, pp. 618-621.
Prepublished online as a Blood First Edition Paper on March 28, 2006; DOI 10.1182/blood-2005-10-4184.
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IMMUNOBIOLOGY
Brief report
Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications
David H. Chang,
Nancy Liu,
Virginia Klimek,
Hani Hassoun,
Amitabha Mazumder,
Stephen D. Nimer,
Sundar Jagannath, and
Madhav V. Dhodapkar
From the Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University; the Hematology Service, Memorial Sloan Kettering Cancer Center; and St Vincent's Cancer Center, New York, NY.
Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Pharmacologic approaches to enhance NKT cell function will facilitate specific NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel thalidomide (Thal) analog, enhances antigen-specific expansion of NKT cells in response to the NKT ligand  -galactosylceramide (-GalCer) in both healthy donors and patients with myeloma. NKT cells activated in the presence of LEN have greater ability to secrete interferon- . Antigen-dependent activation of NKT cells was greater in the presence of dexamethasone (DEX) plus LEN than with DEX alone. Therapy with LEN/Thal also led to an increase in NKT cells in vivo in patients with myeloma and del5q myelodysplastic syndrome. Together these data demonstrate that LEN and its analogues enhance CD1d-mediated presentation of glycolipid antigens and support combining these agents with NKT targeted approaches for protection against tumors.
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