Enhancing the efficacy of near-infrared photoimmunotherapy through intratumoural delivery of CD44–targeting antibody–photoabsorber conjugatesResearch in context
Yuichi Adachi,
Kotaro Miyake,
Kika Ohira,
Shingo Satoh,
Kentaro Masuhiro,
Ryuya Edahiro,
Yuya Shirai,
Maiko Naito,
Yujiro Naito,
Takayuki Shiroyama,
Shohei Koyama,
Haruhiko Hirata,
Kota Iwahori,
Izumi Nagatomo,
Yoshito Takeda,
Atsushi Kumanogoh
Affiliations
Yuichi Adachi
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center, Initiative, Immunology, Frontier Research Center, Osaka University, Osaka, Japan
Kotaro Miyake
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Corresponding author. Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Kika Ohira
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center, Initiative, Immunology, Frontier Research Center, Osaka University, Osaka, Japan
Shingo Satoh
Department of Thoracic Oncology, Osaka Habikino Medical Center, Osaka, Japan
Kentaro Masuhiro
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center, Initiative, Immunology, Frontier Research Center, Osaka University, Osaka, Japan
Ryuya Edahiro
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
Yuya Shirai
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
Maiko Naito
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Yujiro Naito
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center, Initiative, Immunology, Frontier Research Center, Osaka University, Osaka, Japan
Takayuki Shiroyama
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Shohei Koyama
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan
Haruhiko Hirata
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Kota Iwahori
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Izumi Nagatomo
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Yoshito Takeda
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
Atsushi Kumanogoh
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center, Initiative, Immunology, Frontier Research Center, Osaka University, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan; Center for Infectious Diseases for Education and Research, Osaka University, Osaka, Japan; Japan Agency for Medical Research and Development – Core Research for Evolutional Science and Technology, Osaka University, Osaka, Japan; Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan; Corresponding author. Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
Summary: Background: Photoimmunotherapy (PIT) is a potent modality for cancer treatment. The conventional PIT regimen involves the systemic delivery of an antibody–photoabsorber conjugate, followed by a 24-h waiting period to ensure adequate localisation on the target cells. Subsequent exposure to near-infrared (NIR) light selectively damages the target cells. We aimed to improve the efficacy of PIT in vivo by evaluating the effects of the different routes of conjugate administration on treatment outcomes. Methods: Subcutaneous Lewis lung carcinoma tumours were established in mice, targeting cluster of differentiation (CD)44 with an anti-CD44 antibody conjugated to IRDye700DX (IR700). The conjugate was administered via the intravenous or intratumoural route followed by the assessment of antibody binding and therapeutic effects of PIT. Findings: Compared to intravenous administration, intratumoural delivery of the CD44-IR700 conjugate significantly increased the number of cells binding to the conjugate by >five-fold. This method, combined with NIR light irradiation, halved tumour growth when compared to intravenous delivery. Reducing the interval between intratumoural injection and NIR light exposure to 30 min did not diminish efficacy, thereby demonstrating the feasibility of a 1-h procedure. Interpretation: Intratumoural administration of the antibody–photoabsorber conjugate enhanced the efficacy of PIT in vivo. A simplified, 1-h procedure involving conjugate tumour injection followed by irradiation emerged as a potent cancer treatment strategy. Funding: This study was supported by the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development, Japan Science and Technology Agency, and the Osaka Medical Research Foundation for Intractable Diseases.
