Immune checkpoint blockade enhances chemophototherapy in a syngeneic pancreatic tumor model.
APL Bioeng
; 6(3): 036105, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-36164594
ABSTRACT
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 (â¼200 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 (â¼400 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
APL Bioeng
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos