The Immunocytokine F8-IL2 Improves the Therapeutic Performance of Sunitinib in a Mouse Model of Renal Cell Carcinoma

被引：52

作者：

Frey, Katharina

Schliemann, Christoph ^{[3
]}

Schwager, Kathrin ^{[2
]}

Giavazzi, Raffaella ^{[5
]}

Johannsen, Manfred ^{[4
]}

Neri, Dario ^{[1
]}

机构：

[1] ETH, Inst Pharmaceut Sci, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland

[2] ETH, Philochem AG, CH-8093 Zurich, Switzerland

[3] Univ Hosp Munster, Dept Med Hematol Oncol & Pneumol A, Munster, Germany

[4] Charite, Dept Urol, Berlin, Germany

[5] Mario Negri Inst Pharmacol Res, Dept Oncol, I-20156 Milan, Italy

来源：

JOURNAL OF UROLOGY | 2010年 / 184卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

extracellular matrix proteins; carcinoma; renal cell; cytokines; F8 monoclonal antibody; sunitinib; HIGH-DOSE INTERLEUKIN-2; MONOCLONAL-ANTIBODY; VASCULATURE; INTERFERON; DELIVERY; DOMAIN; IDENTIFICATION; FIBRONECTIN; AGENTS; TUMORS;

D O I：

10.1016/j.juro.2010.07.030

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Purpose: We investigated the therapeutic action of F8-IL2, a fusion protein consisting of the F8 antibody specific to the alternatively spliced extradomain-A of fibronectin, in diabody format and of human interleukin-2 in the Caki-1 (ATCC (R)) model of human renal cell carcinoma grafted subcutaneously in nude mice. Materials and Methods: F8-IL2 was cloned, expressed in CHO cells and purified to homogeneity. This immunocytokine was administered alone or combined with 3 standard drugs commonly used as therapy for kidney cancer, including sunitinib, sorafenib and interferon-alpha, in 2 sets of doses and treatment schedules. Results: Neither F8-IL2 nor any other therapeutic agent cured tumor bearing mice when used as a single agent. The best therapeutic results were observed for the combination of sunitinib with F8-IL2 in a continuous administration schedule, which yielded a 28% cure rate and substantial tumor growth retardation. Conclusions: Considering that recombinant interleukin-2 based immunocytokines are now being investigated in several clinical trials in patients with cancer alone or combined with chemotherapy our preclinical results provide a motivation to study F8-IL2 combined with sunitinib in clinical trials in patients with kidney cancer.

引用

页码：2540 / 2548

页数：9

共 31 条

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