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01.04.2009 | Original Article

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

verfasst von: Takeshi Yuasa, Kiyoshi Sato, Eishi Ashihara, Miki Takeuchi, Shinya Maita, Norihiko Tsuchiya, Tomonori Habuchi, Taira Maekawa, Shinya Kimura

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 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.

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Jones SJ, Campbell SC (2006) Non-muscle invasive bladder cancer. In: Kavoussi LR, Novick AC, Partin AW, Peters CA, Wein AJ (eds) Campbell-Walsh Urology, 8th edn. Saunders, New York, pp 2447–2467

Gee J, Sabichi AL, Grossman HB (2002) Chemoprevention of superficial bladder cancer. Crit Rev Oncol Hematol 43:277–286PubMedCrossRef

Herr HW, Laudone VP, Badalament RA, Oettgen HF, Sogani PC, Freedman BD, Melamed MR, Whitmore WF Jr (1988) Bacillus Calmette-Guerin therapy alters the progression of superficial bladder cancer. J Clin Oncol 6:1450–1455PubMed

Ratliff TL, Ritchey JK, Yuan JJ, Andriole GL, Catalona WJ (1993) T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J Urol 150:1018–1023PubMed

Kitamura H, Torigoe T, Honma I, Sato E, Asanuma H, Hirohashi Y, Sato N, Tsukamoto T (2006) Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer. Clin Cancer Res 12:4641–4644PubMedCrossRef

Bubenik J (2003) Tumour MHC class I downregulation and immunotherapy. Oncol Rep 10:2005–2008PubMed

Gober HJ, Kistowska M, Angman L, Jeno P, Mori L, De Libero G (2003) Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med 197:163–168PubMedCrossRef

Kabelitz D, Wesch D, He W (2007) Perspectives of gammadelta T cells in tumor immunology. Cancer Res 67:5–8PubMedCrossRef

Sato K, Kimura S, Segawa H, Yokota A, Matsumoto S, Kuroda J, Nogawa M, Yuasa T, Kiyono Y, Wada H, Maekawa T (2005) Cytotoxic effects of γδ T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy. Int J Cancer 116:94–99PubMedCrossRef

10.

Viey E, Laplace C, Escudier B (2005) Peripheral gammadelta T-lymphocytes as an innovative tool in immunotherapy for metastatic renal cell carcinoma. Expert Rev Anticancer Ther 5:973–986PubMedCrossRef

11.

Halary F, Peyrat MA, Champagne E, Lopez-Botet M, Moretta A, Moretta L, Vié H, Fournié JJ, Bonneville M (1997) Control of self-reactive cytotoxic T lymphocytes expressing gamma delta T cell receptors by natural killer inhibitory receptors. Eur J Immunol 27:2812–2821PubMedCrossRef

12.

Bakker AB, Phillips JH, Figdor CG, Lanier LL (1998) Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL. J Immunol 160:5239–5245PubMed

13.

Kabelitz D, Wesch D, Pitters E, Zöller M (2004) Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T cells in vitro and in SCID mice in vivo. J Immunol 173:6767–6776PubMed

14.

Lozupone F, Pende D, Burgio VL, Castelli C, Spada M, Venditti M, Luciani F, Lugini L, Federici C, Ramoni C, Rivoltini L, Parmiani G, Belardelli F, Rivera P, Marcenaro S, Moretta L, Fais S (2004) Effect of human natural killer and gammadelta T cells on the growth of human autologous melanoma xenografts in SCID mice. Cancer Res 64:378–385PubMedCrossRef

15.

Ichimura Y, Habuchi T, Tsuchiya N, Wang L, Oyama C, Sato K, Nishiyama H, Ogawa O, Kato T (2004) Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J Urol 172:728–732PubMedCrossRef

16.

Nogawa M, Yuasa T, Kimura S, Tanaka M, Kuroda J, Sato K, Yokota A, Segawa S, Toda Y, Kageyama S, Yoshiki T, Okada Y, Maekawa T (2005) Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer. J Clin Invest 115:978–985PubMed

17.

Kimura S, Ito C, Jyoko N, Segawa H, Kuroda J, Okada M, Adachi S, Nakahata T, Yuasa T, Filho VC, Furukawa H, Maekawa T (2005) Inhibition of leukemic cell growth by a novel anti-cancer drug (GUT-70) from Calophyllim brasiliense that acts by induction of apoptosis. Int J Cancer 113:158–165PubMedCrossRef

18.

Nogawa M, Yuasa T, Kimura S, Kuroda J, Sato K, Segawa H, Yokota A, Maekawa T (2005) Monitoring luciferase-labeled cancer cell growth and metastasis in in vivo models. Cancer Lett 217:243–253PubMedCrossRef

19.

Kitamura H, Torigoe T, Honma I, Asanuma H, Nakazawa E, Shimozawa K, Hirohashi Y, Sato E, Sato N, Tsukamoto T (2006) Expression and antigenicity of surviving, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy. Urology 67:955–959PubMedCrossRef

20.

Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, Bajorin DF, Reuter VE, Herr H, Old LJ, Sato E (2007) CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci USA 104:3967–3972PubMedCrossRef

21.

Kimura S, Ashihara E, Maekawa T (2006) New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Curr Pharm Biotechnol 7:371–379PubMedCrossRef

22.

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124PubMedCrossRef

23.

Kato Y, Tanaka Y, Miyagawa F, Yamashita S, Minato N (2001) Targeting of tumor cells for human gammadelta T cells by nonpeptide antigens. J Immunol 167:5092–5098PubMed

24.

van Beek E, Pieterman E, Cohen L, Lowik C, Papapoulos S (1999) Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun 264:108–111PubMedCrossRef

25.

Uchida R, Ashihara E, Sato K, Kimura S, Kuroda J, Takeuchi M, Kawata E, Taniguchi K, Okamoto M, Shimura K, Kiyono Y, Shimazaki C, Taniwaki M, Maekawa T (2007) Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface. Biochem Biophys Res Commun 354:613–618PubMedCrossRef

26.

Sato K, Yuasa T, Nogawa M, Kimura S, Segawa H, Yokota A, Maekawa T (2006) A third generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo. Br J Cancer 95:1354–1361PubMedCrossRef

27.

Kobayashi H, Tanaka Y, Yagi J, Osaka Y, Nakazawa H, Uchiyama T, Minato N, Toma H (2007) Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study. Cancer Immunol Immunother 56:469–476PubMedCrossRef

Titel: Intravesical administration of γδ T cells successfully prevents the growth of bladder cancer in the murine model
verfasst von: Takeshi Yuasa
Kiyoshi Sato
Eishi Ashihara
Miki Takeuchi
Shinya Maita
Norihiko Tsuchiya
Tomonori Habuchi
Taira Maekawa
Shinya Kimura
Publikationsdatum: 01.04.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0571-9

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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

Abstract

Background

Objective

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Objective

Methods

Results

Conclusion

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