584 THERAPEUTIC EFFECT OF INTRAVESICAL ADMINISTRATION OF A NOVEL NANOTRANSPORTER FOR PACLITAXEL IN AN ORTHOTOPIC BLADDER CANCER MODEL

Autor: Eiji Kikuchi, Akira Miyajima, Koetsu Tamura, Mototsugu Oya, Kazuhiro Matsumoto
Rok vydání: 2013
Předmět:
Zdroj: Journal of Urology. 189
ISSN: 1527-3792
0022-5347
Popis: was to examine the potential of intravesical chitosan/IL-12 immunotherapy to eliminate established orthotopic bladder tumors and elicit adaptive, tumor-specific immunity. METHODS: C57BL/6 mice bearing orthotopic MB49 bladder tumors were treated intravesically with saline, IL-12 or chitosan/IL-12 on days 6, 9, and 12 after tumor implantation. Mice eliminating orthotopic MB49 tumors following intravesical chitosan/IL-12 treatment were rechallenged subcutaneously on the flank with MB49 cells or an irrelevant tumor (B16 melanoma). Lymphocytes isolated from cured mice were evaluated for cytotoxic T lymphocyte activity against MB49 or B16 targets. RESULTS: Intravesical chitosan/IL-12 immunotherapy was found to eliminate established tumors in 100% of mice. In addition, all cured mice were protected from a distant MB49 rechallenge, but not B16 challenge. Similarly, lymphocytes from cured mice were found to lyse MB49, but not B16 cells in vitro. Protective immunity was found to be dependent on CD4 and CD8 subsets as their depletion abrogated protection. CONCLUSIONS: These data are the first to show that an intravesical IL-12-based immunotherapy for bladder cancer can induce a systemic tumor-specific immune response. As such, this treatment may be suitable for patients with recurrent superficial disease as well as invasive and metastatic bladder cancers for which there are no effective treatment options.
Databáze: OpenAIRE