Interleukin-21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinoma

✍ Scribed by Hiroshi Nakano; Tsunao Kishida; Hidetsugu Asada; Masaharu Shin-Ya; Takashi Shinomiya; Jiro Imanishi; Taketoshi Shimada; Shigeru Nakai; Minoru Takeuchi; Yasuo Hisa; Osam Mazda

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 217 KB
• Volume: 8
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.817

✦ Synopsis

Background:

Interleukin-21 (il-21) plays important roles in the regulation of t, b, and natural killer (nk) cells. we hypothesized that the cytokine may provide a novel immunotherapy strategy for cancer by stimulating both th1 and th2 immune responses. in this context, antitumor immunity induced by il-21 was examined in mice bearing subcutaneous head and neck squamous cell carcinomas (hnscc).

Methods:

A plasmid vector encoding murine il-21 was injected intravenously into mice with pre-established hnscc tumors, either alone or in combination with a vector construct expressing il-15. cytotoxic t lymphocyte (ctl) and nk killing activities were evaluated by chrome release assays, while hnscc-specific antibody was examined by flow cytometry and elisa.

Results:

Significant antitumor effects were obtained by repeated transfection with either the il-21 or the il-15 gene. co-administration of both cytokine genes resulted in increased suppression of tumor growth, significantly prolonging the survival periods of the animals. thirty percent of the tumor-bearing mice that received the combination therapy survived for more than 300 days, completely rejecting rechallenge with the tumor at a distant site. il-21 induced significant elevation of hnscc-specific ctl activity, while il-21 and il-15 augmented nk activity in an additive manner. il-21 gene transfer also promoted the production of tumor-specific igg.

Conclusions:

In vivo transduction of the il-21 gene elicits powerful antitumor immunity, including both humoral and cellular arms of the immune response, and results in significant suppression of pre-established hnscc. co-transfer of the il-15 gene further improved the therapeutic outcome, mainly by augmenting nk tumoricidal activity. the biological effects of il-21 may be in sharp contrast to those of conventional th1 and th2 cytokines, suggesting intriguing implications of this cytokine for the classical concept of th1 vs. th2 paradigm.