Abstract 4437: Anti-tumor immunotherapeutic strategy for uveal melanoma by combining photodynamic therapy with ROCK inhibitor

Uveal melanoma (UM) is the most frequent intraocular malignant tumor among adults. Although UM is a rare disease, the prognosis of patients with UM is poor since nearly 50% of patients develop metastatic disease, and the overall survival outcome is dismal. Here, we suggest a novel and optimal treatment regime for UM not only offering lower burden to patients with high applicability but also preventing lethal metastatic disease by empowering the immune system through the combination of local Photodynamic therapy (PDT) and ROCK inhibitor. PDT is a topical treatment modality with the minimally invasive therapeutic method and now broadly used in a treatment option for the eyes. PDT with chlorin e6 based formulated FIC elicits immunogenic cell death (ICD) of cancer cells, and hallmarks of ICD stimulate antigen-presenting cells (APCs). Furthermore, ripasudil, one of the ROCK inhibitors, is clinically approved for the treatment of glaucoma and ocular hypertension in the form of an eye drop solution. Ripasudil is repurposed as an anticancer compound based on the immuno-stimulatory effect of ROCK inhibition. A combination of FIC-PDT with ripasudil mediated stimulation of APCs leads primed cytotoxic T cell infiltration into the tumor microenvironment (TME) and eventually augment anti-tumor immunity. Moreover, the combinational strategy sensitizes PD-1/PD-L1 immune checkpoint blockade (ICB) therapy to improve survival rates over time and inhibit tumor growth of the distant tumor by generating a systemic anti-tumor immune response. Collectively, our therapeutic strategy may lead to a new treatment option for UM by suppressing the primary tumor effectively and preventing the metastatic disease.

Citation Format: Seohyun Kim, In-San Kim. Anti-tumor immunotherapeutic strategy for uveal melanoma by combining photodynamic therapy with ROCK inhibitor [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4437.