Immune checkpoint blockade enhances chemophototherapy in a syngeneic pancreatic tumor model

Pancreatic cancer (PaCa) suffers from poor treatment options for locally advanced cases. Chemophototherapy (CPT) is an emerging anti-tumor modality, and porphyrin-phospholipid liposomes have been shown to be versatile drug carriers for CPT in preclinical rodent models. Here we show that in the syngeneic subcutaneous KPC PaCa tumor model, exhausted CD8⁺ T cells are localized in the tumor, and that CPT is enhanced in combination with immune checkpoint blockade (ICB). Addition of ICB using anti-programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies resulted in ablation of medium-sized, established KPC tumors (∼200 mm³) without recurrence for over 100 days. Mice rejected subsequent tumor re-challenge. Flow cytometry and tumor slice analysis following injection of a fluorescently labeled anti-PD-1 antibody showed that CPT improved antibody delivery to the tumor microenvironment. Treatment of large established tumors (∼400 mm³) using with CPT and ICB induced appreciable tumor regression and delay in regrowth. Taken together, these data demonstrate the utility of combining CPT with immunotherapies.