Intravenous administration of a novel IL-2 fusion protein, ALT-801, inhibits bladder cancer in mouse models (46.35)

ALT-801 is a fusion protein between interleukin-2 and a T cell receptor domain capable of recognizing tumors presenting human p53 peptide (aa264-272)/HLA-A*0201 complexes. Previously, we have reported that ALT-801 exhibits significantly better antitumor activity than IL-2 in various mouse tumor models. Substantial efficacy in human malignancies has been observed. In this study, we found that intravenous administration of ALT-801 significantly prolonged survival of C57BL/6 mice bearing MB49luc orthotopic muscle invasive and superficial bladder cancer when compared with PBS treatment. The ALT-801-treated mice also survived rechallenge with MB49luc tumor cells, indicating long-lasting immune response and long-term memory. Additionally, ALT-801 exhibited potent antitumor activity against human bladder cancer HLA-A*0201+/p53+ UMUC-14 and HLA-A*0201-negative/p53+ KU7 xenografts in nude mice, suggesting its targeting activity is not required for efficacy. ALT-801 combined with gemcitabine showed better antitumor effects and less toxicity than gemcitabine + cisplatin (GC) chemotherapy in the UMUC-14 and KU7 xenograft models, despite the different sensitivity of these tumor cells to GC. We’ll discuss the mechanisms of action of ALT-801 in this report. Based on these preclinical findings, we have already initiated a clinical study of ALT-801 on human metastatic bladder cancer.