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Anti-P185 erbB2 scFv-Fc-IL-2 modulates tumor cell surface molecules and activates immune effector cells
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Abstract:
To elucidate the mechanisms by which anti-P185 erbB2 scFv-Fc-IL-2 (HFI) modulates tumor surface molecules and activates immune effector cells in vitro. Methods: Ovarian Cancer Cell Line SKOV3 and human peripheral blood monocyte peripheral blood mononuclear cells (PBMC) were treated with HFI. MTT assay was used to detect the proliferation and cytotoxicity; flow cytometry assay was used to examine expression of surface molecules; bioassay was used to examine cytotoxicity of membrane-associated TNF; and perforin mRNA level was analyzed by RT-PCR assay. Results: HFI had no direct inhibitory effect on proliferation of SKOV3 cells. After HFI treatment, the expression levels of ICAM-1 and Fas on SKOV3 cells rose from 24.85% and 0.53% to 85.36% and 59.19%, respectively （ P <0.01). Besides, HFI significantly enhanced the proliferation of human PBMC. CD3+CD8+ T cells and CD3-CD16+CD56+ T cells rose from 2437% and 6.90% to 38.80% and 13.45%, respectively （ P <0.01). Expression levels of CD25, LFA-1, and FasL significantly increased from 3.99%, 86.52%, and 5.02% to 12.96%, 99.06%, and 16.19%, respectivly（P<0.01). Expression levels of Perforin and membrane-associated TNF were also up-regulated. Cytotoxicities of LAK and NK were both improved（P<0.01). Conclusion: HFI can enhance the expression of ICAM-1 and Fas in SKOV3 cells and has obvious activating effect on PBMC. HFI can up-regulate the expression level of LFA-1/ ICAM-1，Fas/ FasL, promote the release of TNF and perforin, and improve LAK and NK cytotoxicity.
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