Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasis

This study is to investigate the tumor invasion and metastasis inhibition effects of the immunoconjugate composed of lidamycin and anti-type IV collagenase monoclonal antibody Fab' fragment.  Boyden chamber assay was used to evaluate the influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was used to measure the change of invasion factor MMP-2 and MMP-9’s secretion, and RT-PCR was adopted to determine TIMP-1 mRNA expression level.  The immunoconjugate inhibition of tumor in situ metastasis was also tested in nude mice.  The Fab'-LDM conjugates had dose-dependent inhibition effect on HT-1080 cells’ invasion.  At the concentrations of 5 and 10 nmol·L⁻¹, the Fab'-LDM inhibited the invasion by (60 ± 12) % and (79 ± 11) % respectively.  At the concentration of 5 and 10 nmol·L⁻¹, the Fab'-LDM inhibited the secretion of MMP-2 by (42 ± 8) % and (54 ± 6) % and that of MMP-9 by (57 ± 3) % and (87 ± 1) %, respectively.  RT-PCR indicated that conjugates increased the anti-invasion factor TIMP-1 level.  The in vivo experiment showed   that, compared with the control group, the tumor inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 ± 13) %, (86 ± 26) %, (74 ± 22) % respectively.  In conclusion, Fab'-LDM could inhibit the invasion and metastasis of tumor and it might be a new tumor biotherapy agent.