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Biotech / Medical : ZymoGenetics ZGEN -- Ignore unavailable to you. Want to Upgrade?

To: Steve Lokness who wrote (177)	8/28/2009 9:40:51 AM
From: tuck	Respond to of 210

[In vivo antitumor efficacy of interleukin-21 in combination with chemotherapeutics.] >>Cytokine. 2009 Aug 24. [Epub ahead of print] In vivo antitumor efficacy of interleukin-21 in combination with chemotherapeutics. Skak K, Søndergaard H, Frederiksen KS, Ehrnrooth E. Immunopharmacology, Building F6.2.30, Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. Interleukin-21 (IL-21) is a class I cytokine with antitumor properties due to enhanced proliferation and effector function of CD8(+) T cells and natural killer (NK) cells. Here we have explored the magnitude and time-course of cytostatics-induced lymphopenia in mice and investigated whether treatment with cytostatics influences the antitumor effect of IL-21 in mouse tumor models. We show that pegylated liposomal doxorubicin (PLD), irinotecan and oxaliplatin induced transient lymphopenia, whereas 5-fluorouracil (5-FU) transiently increased lymphocyte counts. B cells were more sensitive than T cells towards irinotecan and oxaliplatin. Additive antitumor effects were observed after combining IL-21 with PLD, oxaliplatin and to less extent 5-FU but not irinotecan, and larger effect was observed when IL-21 administration was postponed relative to chemotherapy, suggesting that these agents may transiently impair immune function. However, the chemotherapies did not significantly alter the levels of circulating regulatory T cells and only marginally affected the ability of CD8(+) T cells to respond to IL-21 measured as increased granzyme B mRNA. Our results show that IL-21 therapy can be successfully combined with agents from different chemotherapeutic drug classes, i.e. topoisomerase II inhibitors (PLD), anti-metabolites (5-FU) and platinum analogs (oxaliplatin) provided that IL-21 therapy is delayed relative to chemotherapy.<< Cheers, Tuck