e14544 Background: Although there has been great progress in the early diagnosis of choroidal melanoma, metastases remain the leading cause of cancer-related death. Therefore, improving the treatment efficacy against metastases is essential to enhance patient survival. A new targeted therapy, the virus-like drug conjugate (VDC) AU-011 (belzupacap sarotalocan), is currently in clinical development to treat early-stage choroidal melanoma with an intra-ocular administration followed by near-infrared (NIR) light activation using a photodynamic therapy (PDT) laser. Murine experiments have shown that AU-011 enhances immune checkpoint inhibition (ICI) and protects against tumor rechallenge. Methods: We investigated whether this combination therapy had an effect not only on primary tumors but also on distant, untreated tumors, as a model for treating metastatic cancer by abscopal immune effects and compared the efficacy of combining AU-011 with several ICI antibodies. Results: In vitro, AU-011 treatment induced a preferential cytotoxicity in cancer over antigen presenting cells, confirming the tumor-targeting of AU-011. AU-011 treatment induced immunogenic cell death in several murine cancer cell lines through the release and exposure of damage-associated molecular patterns (DAMPs), resulting in the maturation of dendritic cells. Furthermore, AU-011 in combination with ICI antibodies demonstrated greater efficacy than AU-011 alone, or ICI antibodies alone against established MC38 tumors in mice, resulting in complete tumor response in all treated animals for specific combinations. Finally, AU-011 and anti-PD-L1/ anti-LAG-3 antibody treatment was an optimal combination in an abscopal model of metastatic disease, inducing complete cures in approximately 75 % of animals. Conclusions: Based on our observations, we conclude that AU-011 treatment combined with immune checkpoint inhibition is effective against both primary tumors and distant metastases, and identify anti-PD-L1/ anti-LAG-3 as the most potent combination with AU-011. These data may support an investigation of AU-011 in this combination in future clinical trials.[Table: see text]