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

To: tuck who wrote (124)	6/5/2008 2:34:05 PM
From: tuck	Read Replies (2) \| Respond to of 210

[Interleukin-21 augments the efficacy of T-cell therapy by eliciting concurrent cellular and humoral responses] >>Cancer Res. 2008 Jun 1;68(11):4431-41. Interleukin-21 augments the efficacy of T-cell therapy by eliciting concurrent cellular and humoral responses. Iuchi T, Teitz-Tennenbaum S, Huang J, Redman BG, Hughes SD, Li M, Jiang G, Chang AE, Li Q. Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0666, USA. Interleukin (IL)-21 modulates T-cell-associated, B-cell-associated, and natural killer cell-associated immunity. However, the potential of IL-21 to simultaneously stimulate cellular and humoral antitumor responses and the mechanisms involved have not yet been adequately explored. In this report, we examined the immune-modulating effect of IL-21 when used in vitro and its adjuvant effects when administrated concomitantly with T-cell transfer for cancer therapy. Use of IL-21 in concert with IL-2 in culture up-regulated both type 1 and type 2 cytokine production of activated tumor-draining lymph node cells and enhanced their therapeutic efficacy. Administration of IL-21 and IL-2 as an adjuvant to T-cell transfer resulted in simultaneously elicited cellular and humoral responses. This concurrent response has led to effective regression of established pulmonary metastatic tumors and s.c. tumors. T-cell transfer plus IL-21/IL-2 administration conferred systemic immunity to the treated hosts. This was evident by the induction of protective immunity against tumor rechallenge, expansion of memory T cells, and significantly elevated serum levels of IFN gamma and IL-10. Furthermore, we observed significantly enhanced tumor-associated antibody response after T-cell + IL-2 + IL-21 therapy. Cytotoxic antibody subclass IgG2b increased strikingly in the sera of treated animals; they bound specifically to MCA205 tumor cells, and such immune sera mediated tumor cell lysis in the presence of complement. Use of B-cell-deficient mice provided direct evidence that humoral responses contribute to T-cell + IL-2 + IL-21-elicited antitumor immunity. Collectively, these findings provide a rationale to evaluate the use of IL-21 in T-cell therapy of human cancers.<< MCA205 is a fibrosarcoma (subset of soft tissue sarcoma) cell line. Look out threadsters, I've adjusted my Pubcrawler settings, and from now on PubCrawler will be spitting out ZGEN related abstracts, some of which I will post here. Hope y'all can get used to it. Cheers, Tuck

To: tuck who wrote (124)	3/15/2009 12:58:08 PM
From: tuck	Respond to of 210

[IL-21R P2a melanoma abstract prodies a bit more color] >> Clin Cancer Res. 2009 Mar 10. [Epub ahead of print] Clinical and Biological Efficacy of Recombinant Human Interleukin-21 in Patients with Stage IV Malignant Melanoma without Prior Treatment: A Phase IIa Trial. Davis ID, Brady B, Kefford RF, Millward M, Cebon J, Skrumsager BK, Mouritzen U, Hansen LT, Skak K, Lundsgaard D, Frederiksen KS, Kristjansen PE, McArthur G. Authors' Affiliations: Ludwig Oncology Unit, Austin Health; Cancer Trials Australia; Oncology Research Cabrini Hospital; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sydney Melanoma Unit and Westmead Institute for Cancer Research, University of Sydney, Sydney, New South Wales, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; and Novo Nordisk A/S, Copenhagen, Denmark. PURPOSE: Human interleukin-21 (IL-21) is a class I cytokine that mediates activation of CD8(+) T cells, natural killer (NK) cells, and other cell types. We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma.EXPERIMENTAL DESIGN: Open-label, single-arm, two-stage trial. Eligibility criteria: unresectable metastatic melanoma, measurable disease by Response Evaluation Criteria in Solid Tumors, no prior systemic therapy (adjuvant IFN permitted), adequate major organ function, good performance status, no significant autoimmune disease, and life expectancy at least 4 months. Primary objective: antitumor efficacy (response rate). Secondary objectives: safety, blood biomarkers, and generation of anti-rIL-21 antibodies. rIL-21 (30 microg/kg/dose) was administered by intravenous bolus injection in 8-week cycles (5 dosing days followed by 9 days of rest for 6 weeks and then 2 weeks off treatment).RESULTS: Stage I of the study comprised 14 patients. One confirmed complete response (CR) was observed, and as per protocol, 10 more patients were accrued to stage II (total n = 24: 10 female and 14 male). Best tumor response included one confirmed CR and one confirmed partial response, both with lung metastases. Treatment was overall well tolerated. Biomarker analyses showed increases in serum soluble CD25, frequencies of CD25(+) NK and CD8(+) T cells, and mRNA for IFN-gamma, perforin, and granzyme B in CD8(+) T and NK cells.CONCLUSIONS: rIL-21 administered at 30 microg/kg/d in 5-day cycles every second week is biologically active and well tolerated in patients with metastatic melanoma. Confirmed responses, including one CR, were observed.<< Cheers, Tuck