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  • Title: Rituximab-mediated antibody-dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by interleukin-2.
    Author: Golay J, Manganini M, Facchinetti V, Gramigna R, Broady R, Borleri G, Rambaldi A, Introna M.
    Journal: Haematologica; 2003 Sep; 88(9):1002-12. PubMed ID: 12969808.
    Abstract:
    BACKGROUND AND OBJECTIVES: We analyzed the sensitivity of freshly isolated neoplastic B cells to rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC), using different effector cells. DESIGN AND METHODS: ADCC was performed by 51Cr release assays in vitro, using peripheral blood mononuclear cells, IL-2-activated or expanded NK cells, neutrophils or macrophages as effector cells. B lymphoma lines and freshly isolated leukemic samples were used as targets. RESULTS: NK cells, but PMN or macrophages mediated rituximab dependent cellular cytotoxicity against two B lymphoma lines. Purified NK cells (95% CD56+/CD16+) reached 70% lysis at the highest E:T ratio. By contrast, all freshly isolated B leukemia or lymphoma cases, including 5 chronic lymphocytic leukemia, 1 B-prolymphocytic leukemia, 1 mantle cell lymphoma, 2 marginal zone lymhomas and 2 follicular lymphomas were poorly lysed by ADCC in the same conditions and regardless of CD20 expression levels, reaching a mean of 4% and 27% maximal lysis with PBMC or purified NK cells, respectively. Interestingly, short term IL-2 cultured PBMC, containing 10 % activated NK cells, as well as long-term expanded NK cells, containing 80-95% activated NK cells, became strong ADCC effector cells with rituximab and lysed all leukemic samples to a mean of 57% and 67% at the highest E:T ratio, respectively. INTERPRETATION AND CONCLUSIONS: Primary leukemic cells are more resistant than cell lines to rituximab- and NK cell-mediated ADCC but short-term exposure to IL-2 or long-term expansion of NK cells in vitro may provide effective tools to improve the therapeutic activity of rituximab.
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