Luciferase Reporter Cell Line - OVCAR3

To eradicate residual peritoneal lesions following primary cytoreductive surgery, there is an urgent need to develop more effective therapeutic strategies for ovarian cancer. Here, researchers evaluated the efficacy of targeted alpha-particle therapy (TAT) for HER2-positive ovarian cancer, utilizing trastuzumab as a carrier to deliver Pb-214/Bi-214 in a mouse model harboring residual lesions. The density of HER2 receptors on the surface of SKOV3 cells was determined to be 590,000 ± 5,500 receptors per cell, whereas OVCAR3 cells possessed only 7,900 ± 770 receptors per cell. In vitro clonogenic assays performed on SKOV3 cells demonstrated that, compared to the control group, treatment with Pb-214/Bi-214-TCMC-trastuzumab resulted in a significant reduction in the cells' clonogenic potential. Nude mice bearing luciferase-expressing SKOV3 or OVCAR3 tumors were administered either Pb-214/Bi-214-TCMC-trastuzumab or the corresponding control treatments. Compared to the three control groups, two doses of 0.74 MBq of Pb-214/Bi-214-TCMC-trastuzumab significantly inhibited the growth of SKOV3 tumors over a 60-day period, with no observed signs of toxicity. For mice bearing OVCAR3 tumors, the administration of two doses of 0.74 MBq of either Pb-214/Bi-214-TCMC-trastuzumab or Pb-214/Bi-214-TCMC-IgG1 yielded effective therapeutic outcomes without inducing toxicity. Collectively, these data demonstrate that Pb-214/Bi-214-generated via an Rn-222 generator system-has been successfully applied in targeted alpha-particle therapy (TAT), and that Pb-214/Bi-214-TCMC-trastuzumab exhibits significant therapeutic efficacy in murine xenograft tumor models.

In this study, luciferase-expressing OVCAR-3 cells were implanted via intraperitoneal injection into female Balb/c nude mice. The nude mice with OVCAR3 tumors were treated with two doses of 0.74 MBq Pb-214/Bi-214-TCMC-Trastuzumab/IgG on days 1 and 9 (Figure 1A). Compared to the untreated control group, both the groups treated with Pb-214/Bi-214-TCMC-Trastuzumab and Pb-214-TCMC-IgG demonstrated a significant retardation of tumor growth (Figure 1B and C). By the end of the study, the bioluminescence signal in the untreated mice had increased to 254% of the initial level; in contrast, the groups treated with Pb-214/Bi-214-TCMC-Trastuzumab and Pb-214/Bi-214-TCMC-IgG showed increases in bioluminescence signals of only 57% and 77%, respectively. Overall, the growth rate of OVCAR-3 tumors was slower than that of SKOV3 tumors.

Figure 1. Fractionated intraperitoneal treatments of Pb-214/Bi-214-TCMC-Trastuzumab suppress peritoneal human OVCAR3 ovarian tumor growth in a nude mouse model. (Metebi A, et al., 2024)