Rapamycin verhindert Abstossung und Tumorwachstum in einem Tumor-Transplantations-Modell in der Maus

Abstract

Immunosuppressive therapy in transplantation remains rather unspecific with known side effects of a generally suppressed immune system. Studies provided clear evidence for an increased susceptibility for infections and also cancer in the immunosuppressed patient population. One possible way to address this problem is the discovery of agents with both immunosuppressive and anti-cancer properties. Here, we tested the effect of rapamycin versus cyclosporine on tumor growth and graft survival in transplanted mice simultaneously bearing tumors. In one model, C57B1/6 mice received subcutaneous implants of syngenic B16 melanoma cells; 7 days later a vascularized heterotopic C3H heart transplant was performed. In a second model, BALB/ c mice received subcutaneous syngenic CT-26 colon adenocarcinoma cells 7 days before C3H “ear-heart” transplantation. Rapamycin or cyclosporine treatment was initiated also on day 7 after tumor-implantation. In the C57B1/6 model, B16 tumors grew for 2–3 weeks before mice died from tumor complications. However, rapamycin treatment protected allografts, permitted animal survival, and inhibited tumor growth. In contrast, cyclosporine-treated mice died from advancing tumors, albeit, with a functioning allograft. Similar findings were observed with CT-26 tumors and “ear-heart”-transplants in Balb/c mice.