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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2009

01-04-2009 | Original Article

Intravesical administration of γδ T cells successfully prevents the growth of bladder cancer in the murine model

Published in: Cancer Immunology, Immunotherapy | Issue 4/2009

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Abstract

Background

Superficial bladder cancers are usually managed with transurethral resection followed by the intravesical administration of Bacillus Calmette-Guerin which requires major histocompatibility complex (MHC) class I expression on cancer cells. Since cancer cells often loose MHC expression, a novel immunotherapy such as MHC-unrestricted γδ T cell therapy is desired.

Objective

To clarify the relationship between the expression of MHC class I and clinicopathological features in bladder cancer patients, and investigate the effects of the administration of intravesical γδ T cells on bladder cancer.

Methods

Samples from 123 patients who had undergone either transurethral resection or radical cystectomies were examined for MHC expression and the relationship between this and the clinicopathological features was analyzed statistically. The in vitro and in vivo effects of γδ T cells expanded by zoledronic acid (ZOL) against several types of cancer cell line and an orthotopic bladder cancer murine model which was pretreated with ZOL were investigated.

Results

MHC-diminished superficial bladder cancer was significantly more progressive than MHC-conservative bladder cancer (P = 0.047). In addition, there was a significant association between diminished MHC expression and poor disease free survival (P = 0.041) and overall survival (P = 0.018) after radical cystectomy. In vitro, all of the cell lines pretreated with 5-μM ZOL showed a marked increase in sensitivity to lysis by γδ T cells. Moreover, intravesical administration of γδ T cells with 5-μM ZOL significantly demonstrated antitumor activity against bladder cancer cells in the orthotopic murine model (P < 0.001), resulting in prolonged survival.

Conclusion

The present murine model provides a potentially interesting option to develop immunotherapy using γδ T cells for bladder cancer in human.
Appendix
Available only for authorised users
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Metadata
Title
Intravesical administration of γδ T cells successfully prevents the growth of bladder cancer in the murine model
Publication date
01-04-2009
Published in
Cancer Immunology, Immunotherapy / Issue 4/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0571-9

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