转移瘤仍然是全球癌症相关死亡的主要原因。因此，提高对这些肿瘤的治疗效果对增强患者的生存至关重要。AU-011（belzupacap sarotalocan）是一种新型病毒类药物结合物，目前正在临床开发中，用于治疗眼部小脉络膜黑色素瘤和高危不定性病变。在光照激活下，AU-011引发快速坏死性细胞死亡，具有促炎性和促免疫原性，导致抗肿瘤免疫反应。由于已知AU-011能诱导全身性抗肿瘤免疫反应，因此我们研究了这种联合治疗是否也对未经治疗的远处肿瘤有效，作为通过抗肿瘤免疫效应治疗局部和远处肿瘤的模型。我们比较了将AU-011与几种不同的抑制剂抗体相结合的疗法的有效性，以确定最佳治疗方案，在体内肿瘤模型中。我们展示了AU-011通过释放和暴露损伤相关分子模式（DAMPs）诱发免疫原性细胞死亡，导致体外树突状细胞成熟。此外，我们展示了AU-011随时间在MC38肿瘤中的积累和ICI增强了AU-011对小鼠中已建立肿瘤的疗效，在所有携带单个MC38肿瘤的治疗动物中，特定组合使其完全消失。最后，我们展示了AU-011和抗PD-L1 /抗LAG-3抗体治疗在体外作为抗肿瘤效应最佳组合，在约75％的动物中诱导完全消失。我们的数据显示，AU-011与PD-L1和LAG-3抗体的联合治疗可行，用于治疗原发性和远处肿瘤。 ©2023。作者（们）。

Metastases remain the leading cause of cancer-related death worldwide. Therefore, improving the treatment efficacy against such tumors is essential to enhance patient survival. AU-011 (belzupacap sarotalocan) is a new virus-like drug conjugate which is currently in clinical development for the treatment of small choroidal melanoma and high-risk indeterminate lesions in the eye. Upon light activation, AU-011 induces rapid necrotic cell death which is pro-inflammatory and pro-immunogenic, resulting in an anti-tumor immune response. As AU-011 is known to induce systemic anti-tumor immune responses, we investigated whether this combination therapy would also be effective against distant, untreated tumors, as a model for treating local and distant tumors by abscopal immune effects. We compared the efficacy of combining AU-011 with several different checkpoint blockade antibodies to identify optimal treatment regimens in an in vivo tumor model. We show that AU-011 induces immunogenic cell death through the release and exposure of damage-associated molecular patterns (DAMPs), resulting in the maturation of dendritic cells in vitro. Furthermore, we show that AU-011 accumulates in MC38 tumors over time and that ICI enhances the efficacy of AU-011 against established tumors in mice, resulting in complete responses for specific combinations in all treated animals bearing a single MC38 tumor. Finally, we show that AU-011 and anti-PD-L1/anti-LAG-3 antibody treatment was an optimal combination in an abscopal model, inducing complete responses in approximately 75% of animals. Our data show the feasibility of combining AU-011 with PD-L1 and LAG-3 antibodies for the treatment of primary and distant tumors.© 2023. The Author(s).