Adrenocortical carcinoma (ACC) is a rare endocrine
tumor entity with poor prognosis. Medical treatment is limited to common
cytotoxic agents, which are associated with low treatment responses. Thus, lack of therapeutic efficacy demands innovative treatment options for patients with advanced ACC. Recently, we have developed and characterized anti-IGF1 receptor (IGF1-R) immunoliposomes (SSLD-1H7) for the treatment of
neuroendocrine tumors of the gastroenteropancreatic system. As previous results indicated putative applicability also for other IGF1-R-overexpressing
tumor entities, we initiated testing of liposomal preparations in in vitro and in vivo models of ACC. Adrenocortical NCIh295 cells were used for in vitro association studies with different liposomal formulations. Thereby, flow cytometry revealed high cellular association and internalization of anti-IGF1-R immunoliposomes (soy
phosphatidylcholine (SPC)/
cholesterol (Chol)-polyethyleneglycol (PEG)-1H7, 50.1±2.2%). Moreover, internalization of pegylated
liposomes (SPC/Chol-PEG, 57.1±2.4%) and an even higher uptake of plain
liposomes (84.6±0.8%; P<0.0001) were detectable in adrenocortical
tumor cells. In vivo, liposomal treatments were investigated on NCIh295
tumor xenografts in pharmacokinetic and therapeutic experiments. A significant reduction in
tumor size was detectable in NCIh295
tumor-bearing mice after a single treatment with SSLD-1H7 (0.89±0.15 cm; P=0.006) and a diminished efficacy for SSLD-PEG+ (1.01±0.19 cm; P=0.04) in comparison with untreated controls (1.5±0.0 cm). Thus, anti-IGF1-R immunoliposomes have been successfully tested in vitro and in vivo in a preclinical model for ACCs and could, therefore, represent a promising therapeutic approach for this
tumor entity. Moreover, a combination of
mitotane plus liposomally encapsulated
cytostatic agents instead of free drugs could also be an interesting novel treatment option for ACC in the future.