title: Photoimmunotherapy: comparative effectiveness of two monoclonal antibodies targeting the epidermal growth factor receptor.
abstract: Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two commonly available anti-EGFR monoclonal antibodies, cetuximab and panitumumab, for their effectiveness as PIT agents in EGFR positive tumor models. A photosensitizer, IR-700, conjugated to either cetuximab (cet-IR700) or panitumumab (pan-IR700), was evaluated using EGFR-expressing A431 and MDAMB468-luc cells in 2D- and 3D-culture. PIT was conducted with irradiation of NIR light after exposure of the sample or animal to each conjugate. In vivo PIT was performed with fractionated exposure of NIR light after injection of each agent into A431 xenografts or a MDAMB468-luc orthotopic tumor bearing model. Cet-IR700 and pan-IR700 bound with equal affinity to the cells in 2D-culture and penetrated equally into the 3D-spheroid, resulting in identical PIT cytotoxic effects in vitro. In contrast, in vivo anti-tumor effects of PIT with cet-IR700 were inferior to that of pan-IR700. Assessment of the biodistribution showed lower accumulation into the tumors and more rapid hepatic catabolism of cet-IR700 compared to pan-IR700. Although cet-IR700 and pan-IR700 showed identical in vitro characteristics, pan-IR700 showed better therapeutic tumor responses than cet-IR700 in in vivo mice models due to the prolonged retention of the conjugate in the circulation, suggesting that retention in the circulation is advantageous for tumor responses to PIT. These results suggest that the choice of monoclonal antibody in photosensitizer conjugates may influence the effectiveness of PIT.
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Kazuhide
authors: K
authors: Sato
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Rira
authors: R
authors: Watanabe
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Hirofumi
authors: H
authors: Hanaoka
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Toshiko
authors: T
authors: Harada
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Takahito
authors: T
authors: Nakajima
authors: Applied/Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick, MD 20892, United States.
authors: Insook
authors: I
authors: Kim
authors: Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, MD 20892, United States.
authors: Chang H
authors: CH
authors: Paik
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States.
authors: Peter L
authors: PL
authors: Choyke
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, MD 20892, United States. Electronic address: Kobayash@mail.nih.gov.
authors: Hisataka
authors: H
authors: Kobayashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D000077544:Panitumumab; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010789:Phototherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017319:Photosensitizing Agents; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Epidermal growth factor receptor; Monoclonal antibody; NIR-fluorescence; Pharmacokinetics; Photoimmunotherapy