| Epithelial ovarian cancer remains the leading cause of death from gynecologic maligncies. Because of the lack of the effective screening methods and the vague symptoms associated with early stage disease, most patients with epithelial ovarian cancer present with an advanced stage of the disease. Although surgical debulking and combination chemotherapy produce good, short-term results, most tumors will recur and second-line therapies have not proven to provide cures in all cases. Given these outcomes, new treatments have been developed. Bispecific antibody(BsAb) are regarded as powerful tools for the immunological treatment of malignant cells in a minimal residual disease situation. BsAb comprise two specificities and can redirect effector cells towards therapeutic targets. These molecules can limit complement activation, which is responsible for side effects in many theraputic setting, and profoundly enhance target selectivity.A bispecific-single-chain antibody, BHL-I, that could retarget human T cells to destroy human ovarian carcinoma had been constructed by genetic engineering and expressed in E. coli.In this paper, molecular characteristics, binging properties, and ability to retarget T cells were studied. BHL-I was capable of binding to human CD3 and human ovarian cancer as detected by ELISA and by FACS analysis of T cells and SKOV3 cells, respectively. It could also bridge activated human T cells and human ovarian carcinoma as demonstrated by a bridge FACS assay. Redirected human T cells could mediate human target cell lysis in a MTT assay in vitro. In vivo, a radioimmunoimaging(RII) assay verified that BHL-I can target to tumor sites specificity.The results showed BHL-I can be used as a preclinical immunotheraputic model for human ovarian cancer. |
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