[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 |
