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  • Title: A caspase-6 and anti-HER2 antibody chimeric tumor-targeted proapoptotic molecule decreased metastasis of human osteosarcoma.
    Author: Wang LF, Zhou Y, Xu YM, Qiu XC, Zhou BG, Wang F, Long H, Chen X, Yang TT, Ma BA, Fan QY, Yang AG.
    Journal: Cancer Invest; 2009 Aug; 27(7):774-80. PubMed ID: 19488908.
    Abstract:
    Human growth factor receptor-2 (HER2), overexpressed as a result of gene amplification, is detected in 20-40% of patients with breast, ovarian, endometrial, gastric, bladder, prostate, or lung cancers, correlated to metastasis of many tumors, and considered to be a poor prognostic indicator for these tumors. However, the data was controversial for HER2 overexpression and the prognosis of osteosarcoma, which is the most common primary malignant bone tumor, presents a therapeutic challenge in medical oncology due to its metastasis and poor response to current treatments. Previously, we reported that the immunocasp-6 gene fused by a HER2-specific single-chain antibody with domain II of Pseudomonas exotoxin A (PEA) and the 5' end of the truncated active caspase-6 could selectively suppress the HER2-positive tumor growth. In this study, we extend its application. We first confirmed the higher HER2 expression on the surface of metastatic osteosarcoma SOSP-9607(E10) cells, which then be proved specifically addicted to immunocasp-6-induced cells killing in vitro. Thereafter, the efficacy of immunocasp-6 was tested in an osteosarcoma lung metastasis mouse model using intramuscular (i.m.) injections of liposome-encapsulated vectors. Our results showed that the expression of the immunocasp-6 gene not only significantly prolonged animal's survival, but also greatly inhibited tumor metastasis. Thereby, our strategy suggests an alternative approach to treating HER2/neu-positive osteosarcoma.
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