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Interleukin-21 Gene Transfection Into Mouse Bladder Cancer Cells Results in Tumor Rejection Through the Cytotoxic T Lymphocyte Response

Interleukin-21 Gene Transfection Into Mouse Bladder Cancer Cells Results in Tumor Rejection Through the Cytotoxic T Lymphocyte Response

Junya Furukawa, Isao Hara, Hiroshi Nagai, Akihisa Yao, Shuntaro Oniki, Masato Fujisawa

J Urol. 2006 Sep;176(3):1198-203.

PMID: 16890725

Abstract:

Purpose:
We developed the genetically modified mouse bladder carcinoma MBT2 (American Type Culture Collection, Manassas, Virginia), which secretes interleukin-21, to investigate the functional activities of interleukin-21 in tumor immunity.
Materials and methods:
The IL-21 gene was cloned from activated T cells by reverse transcriptase-polymerase chain reaction, inserted into an expression vector and then introduced into MBT2 using Lipofectamine. Exogenous interleukin-21 was assayed in culture supernatants from transfectants using sandwich enzyme-linked immunoassay. Direct antitumor and tumor vaccine effects were investigated in syngeneic mice rendered immunodeficient by administration of the corresponding antibody.
Results:
MBT2 cells secreting interleukin-21 (MBT2/IL-21) were completely rejected when subcutaneously injected into syngeneic mice. MBT2/IL-21 proliferated only when CD8+ T cells were depleted, whereas MBT2/IL-21 proliferation was totally abrogated in mice depleted of CD4+ T cells, natural killer cells or interferon-gamma. Subcutaneous injection of MBT2/IL-21 treated with mitomycin C remarkably inhibited parental MBT2 tumor growth at the contralateral site. Cytotoxicity assays using splenocytes from mice that rejected MBT2/IL-21 and the immunohistochemical features of MBT2/IL-21 tumors confirmed that in situ production of interleukin-21 can elicit powerful antitumor activity through CD8+ T-cell activation.
Conclusions:
Interleukin-21 production in situ elicits antitumor activity through the activation of CD8+ T cells in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413381	Interleukin-21 from mouse			Price

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