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Japanese Journal of Clinical Oncology Advance Access originally published online on March 31, 2009
Japanese Journal of Clinical Oncology 2009 39(5):303-309; doi:10.1093/jjco/hyp021
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© The Author (2009). Published by Oxford University Press. All rights reserved

Antitumor Efficacy of Recombinant Human Interleukin-2 Combined with Sorafenib Against Mouse Renal Cell Carcinoma

Motofumi Iguchi1, Mitsunobu Matsumoto1, Kanji Hojo1, Toru Wada1, Yoshiyuki Matsuo1, Akinori Arimura1,2 and Kenji Abe1

1 Discovery Research Laboratories
2 Strategic Development Department, Shionogi & Co., Ltd., Osaka, Japan

For reprints and all correspondence: Kenji Abe, Discovery Research Laboratories, Shionogi & Co., Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. E-mail: kenji.abe{at}shionogi.co.jp

Received December 17, 2008; accepted February 20, 2009

Objective: Recombinant human interleukin-2 (rhIL-2) has been clinically used in the treatment of renal cell carcinoma (RCC). Sorafenib, a multi-targeted kinase inhibitor, has been approved for RCC as well as IL-2. The purpose of this study was to evaluate the antitumor efficacy of IL-2 combined with sorafenib in three different murine renal cancer models using Renca cells.

Methods: We established the subcutaneous tumor model by inoculating wild-type Renca cells into the backs of BALB/c mice, the pulmonary metastatic tumor model by an intravenous injection of luciferase-expressing Renca cells into the tail vain and the orthotopic tumor model by injecting luciferase-expressing Renca cells into the renal subcapsule. These tumor-bearing mice were treated intra-peritoneally with rhIL-2 and/or per os with sorafenib. The antitumor efficacy was evaluated by measuring the tumor size of the subcutaneous tumor or photon intensity of the pulmonary metastatic tumor and the orthotopic tumor.

Results: When rhIL-2 was combined with sorafenib, the antitumor efficacy was significantly augmented in comparison with either rhIL-2 or sorafenib alone in all the models. Sorafenib did not inhibit rhIL-2-induced natural killer cell expansion and rhIL-2 had no effect on the anti-angiogenic activity of sorafenib.

Conclusions: The results suggest that the combination of rhIL-2 and sorafenib may offer significant potential as a novel therapeutic approach for patients with RCC.

Key Words: IL-2 • sorafenib • combination therapy • renal cell carcinoma


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 Jpn J Clin OncolHome page
Y. Amagai, M. Matsumoto, K. Hojo, M. Iguchi, T. Wada, H. Tanaka, N. Ide, A. Kato, M. Shichijo, and K. Abe
Combination Therapy of Interleukin-2 and Sorafenib Improves Survival Benefits and Prevents Spontaneous Pulmonary Metastasis in Murine Renal Cell Carcinoma Models
Jpn. J. Clin. Oncol., January 27, 2010; (2010): hyp200v1 - hyp200.
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