PD-L1 near Infrared Photoimmunotherapy of Ovarian Cancer Model

SIMPLE SUMMARY: Ovarian cancer is one of the leading causes of cancer-related death among women in the United States. Overall survival of patients with advanced stage disease has not significantly changed despite improvements in treatment that have extended median survival. Photoimmunotherapy (PIT) using an antibody conjugated to a near infrared (NIR) dye constitutes an effective theranostic strategy to detect and selectively eliminate cell populations. The programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway is being extensively studied for immune checkpoint blockade. PD-L1 expression has been described across all major ovarian cancer histological subtypes and is commonly expressed by cancer cells and by tumor-associated macrophages (TAMs). Here, we used NIR-PIT to eliminate PD-L1-expressing TAMs and cancer cells in ovarian cancer xenografts. Overall, our findings support using NIR-PIT as a potential therapeutic option for ovarian cancer. ABSTRACT: (1) Background: Despite advances in surgical approaches and drug development, ovarian cancer is still a leading cause of death from gynecological malignancies. Patients diagnosed with late-stage disease are treated with aggressive surgical resection and chemotherapy, but recurrence with resistant disease is often observed following treatment. There is a critical need for effective therapy for late-stage ovarian cancer. Photoimmunotherapy (PIT), using an antibody conjugated to a near infrared (NIR) dye, constitutes an effective theranostic strategy to detect and selectively eliminate targeted cell populations. (2) Methods: Here, we are targeting program death ligand 1 (PD-L1) using NIR-PIT in a syngeneic mouse model of ovarian cancer. PD-L1 PIT-mediated cytotoxicity was quantified in RAW264.7 macrophages and ID8-Defb29-VEGF cells in culture, and in vivo with orthotopic ID8-Defb29-VEGF tumors. (3) Results: Treatment efficacy was observed both in vitro and in vivo. (4) Conclusions: Our data highlight the need for further investigations to assess the potential of using NIR-PIT for ovarian cancer therapy to improve the treatment outcome of ovarian cancer.