Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody.

Abstract

Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro. In the in vivo study, avelumab-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of avelumab-IR700 i.v.; (3) NIR light exposure only, NIR light was administered; (4) 100 μg of avelumab-IR700 i.v., NIR light was administered. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.01 vs other groups). In conclusion, the anti-PD-L1 antibody, avelumab, is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with avelumab-IR700 is a promising candidate of the treatment of PD-L1-expressing tumors that could be readily translated to humans.

• Authors: Tadanobu Nagaya, Yuko Nakamura, Kazuhide Sato, Toshiko Harada, Peter L Choyke, James W Hodge, Jeffrey Schlom, Hisataka Kobayashi
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 5 Pg. 8807-8817 (Jan 31 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 27716622 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• Fluorescent Dyes
• avelumab

Topics

• Adenocarcinoma (immunology, metabolism, pathology, therapy)
• Adenocarcinoma of Lung
• Adenocarcinoma, Papillary (immunology, metabolism, pathology, therapy)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological (pharmacology)
• B7-H1 Antigen (antagonists & inhibitors, immunology, metabolism)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Female
• Fluorescent Dyes (pharmacology)
• Humans
• Immunotherapy (methods)
• Infrared Rays
• Lung Neoplasms (immunology, metabolism, pathology, therapy)
• Mice, Nude
• Phototherapy (methods)
• Time Factors
• Tumor Burden
• Xenograft Model Antitumor Assays