title: 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.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000231:Adenocarcinoma, Papillary / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007259:Infrared Rays; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D010789:Phototherapy / Q000379:methods*; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D005456:Fluorescent Dyes; C000609138:avelumab
keywords: PD-L1; lung cancer; near infrared photoimmunotherapy