Interleukin-12 immunotherapy of murine transitional cell carcinoma of the bladder: dose dependent tumor eradication and generation of protective immunity

Michael A O'Donnell; Yi Luo; Sharon E Hunter; Xiaohong Chen; Lori L Hayes; Steven K Clinton

doi:10.1097/01.ju.0000109742.88380.a2

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Interleukin-12 immunotherapy of murine transitional cell carcinoma of the bladder: dose dependent tumor eradication and generation of protective immunity

Journal article

Peer reviewed

Interleukin-12 immunotherapy of murine transitional cell carcinoma of the bladder: dose dependent tumor eradication and generation of protective immunity

Michael A O'Donnell, Yi Luo, Sharon E Hunter, Xiaohong Chen, Lori L Hayes and Steven K Clinton

The Journal of urology, Vol.171(3), pp.1330-1335

03/2004

DOI: 10.1097/01.ju.0000109742.88380.a2

PMID: 14767343

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Abstract

The antitumor activity of interleukin (IL)-12 has been demonstrated in a number of tumor models but barely tested in bladder cancer models. We evaluated the antibladder cancer activity of this cytokine in syngeneic mice bearing subcutaneous, metastatic and orthotopic tumors. Mice were implanted subcutaneously, intravenously or orthotopically with syngeneic transitional cell carcinoma (TCC) of the bladder. The tumor bearing mice were then treated with IL-12 locally or systemically and monitored for tumor regression and survival. In the subcutaneous model dose dependent suppression of tumorigenesis was observed when IL-12 was administered subcutaneously at a distal site with the MB49 line being more sensitive than MBT-2. IL-12 (10 days) above 50 ng daily was tumor inhibitory, while doses of 500 or 1000 ng daily prolonged survival and cured 70% and 75% of subjects, respectively. Upon re-challenge with parental tumor cells mice previously cured with IL-12 (1000 vs 500 ng daily) exhibited specific protection (70% vs 35% rejection) that was dependent on the earlier dose of cytokine. IL-12 administered intraperitoneally at a dose of 250 ng daily was more potent than subcutaneous administration and complete regression was observed. Metastatic TCC in the lungs and orthotopic tumors in the bladder also favorably responded to systemic or intravesical IL-12 therapy, respectively. Addition of IL-2 to IL-12 therapy increased tumor regression, long-term survival and rejection of re-challenged parental tumor. IL-12 is exceptionally effective for treating murine bladder TCC in subcutaneous, metastatic and orthotopic models. The antibladder cancer activity of this cytokine should be tested in human bladder cancer therapy.

Carcinoma, Transitional Cell - mortality

Neoplasm Transplantation

Urinary Bladder Neoplasms - mortality

Mice, Inbred C57BL

Survival Rate

Urinary Bladder Neoplasms - drug therapy

Remission Induction

Mice, Inbred C3H

Dose-Response Relationship, Drug

Animals

Carcinoma, Transitional Cell - immunology

Carcinoma, Transitional Cell - drug therapy

Urinary Bladder Neoplasms - immunology

Female

Interleukin-12 - therapeutic use

Mice

Details

Title: Subtitle: Interleukin-12 immunotherapy of murine transitional cell carcinoma of the bladder: dose dependent tumor eradication and generation of protective immunity
Creators: Michael A O'Donnell - Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA. odonnell@uiowa.edu
Yi Luo
Sharon E Hunter
Xiaohong Chen
Lori L Hayes
Steven K Clinton
Resource Type: Journal article
Publication Details: The Journal of urology, Vol.171(3), pp.1330-1335
Publisher: United States
DOI: 10.1097/01.ju.0000109742.88380.a2
PMID: 14767343
ISSN: 0022-5347
eISSN: 1527-3792
Grant note: R29 CA64230 / NCI NIH HHS K07 CA23326 / NCI NIH HHS
Language: English
Date published: 03/2004
Academic Unit: Urology
Record Identifier: 9984051774202771

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