Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line

C57BL/6J mice were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous injection once a week. Prior to ninth vaccination, the mice were challenged with B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor growth model or by tail venous injection for the lung metastasis model. Development of subcutaneous tumor and lung metastasis was monitored by computed tomography scanning, which enabled accurate evaluation with the minimized sacrifice of mice.Vaccination with Tpit/E cells inhibited subcutaneous tumor growth and appearance of lung metastasis compared to control. Survival period was elongated in the Tpit/E vaccination in both of the two models. We also obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse vaccinated with the cells, indicating that specific immune response to the syngeneic endothelial cells was elicited.These results suggest that vaccination with an autologous endothelial cell line may be effective against melanoma.Cancer immunotherapy has now gained importance as therapeutics especially for cancers resistant to surgery, chemotherapy or radiation therapy. Previously, we have shown that melanoma patients vaccinated with tumor lysate pulsed-dendritic cells elicited antibody response to carbonic anhydrase II of which expression was specific to tumor endothelial cells [1]. Angiogenesis has been shown to play a key role in tumor growth and metastasis and new molecules targeting tumor angiogenesis have been discovered and coming into clinical use [2-5]. These findings have led us to investigate cancer vaccine therapy targeting tumor angiogenesis.Efficacy of immunotherapy targeting known molecules associated in tumor angiogenesis such as VEGF [6], VEGFR-2 [7-10], FGF-2 [11], FGFR-1 [12], endoglin [13], Tie-2 [14], HP59 [15], survivin [16], matrix metalloproteinase [17], integrin beta3 [18], vascular endothelial-cadherin [19], angiomotin [20], and angiopoietin-2 [21] have been reported. Ma