Antibody-selective elimination of drug-resistant pathogens with near-infrared light

• Project/Area Number: 17K16233
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: ITO KIMIHIRO 東京慈恵会医科大学, 医学部, 助教 (60794336)
• Research Collaborator: MITSUNAGA Makoto (40433990) ; IWASE Tadayuki (80385294) ; NISHIMURA Takashi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 薬剤耐性菌 / 分子標的薬 / 近赤外光 / 光免疫療法 / 感染症治療学 / 光線免疫療法

Outline of Final Research Achievements

We have recently developed photoimmunotherapy (PIT) as a new class of molecular targeted cancer therapy based on the conjugation of a monoclonal antibody (mAb) with a near-infrared (NIR) light-activated photosensitizer (PS). The mAb-PS conjugate binds immunospecifically to the target molecules on the cancer cell surface and rapidly ruptures the membrane after NIR light exposure. Here, we conducted a proof of concept study of PIT against pathogens utilizing mAb-PS conjugates by targeting the cell wall component of Staphylococcus aureus. S. aureus targeting mAb-PS conjugate selectively binds and kills S. aureus upon NIR light exposure irrespective of the antibiotic resistance both in in vitro and in vivo models.

Academic Significance and Societal Importance of the Research Achievements

ペニシリンが実用化されてから、細菌感染症に対する治療は抗菌薬の進歩と耐性菌の出現を繰り返している。近年になり、複数の耐性メカニズムを持つ細菌も検出されるようになり、薬剤耐性菌に対する感染症治療は全世界的な問題である。今回開発した病原体に対するPITは、細菌の主たる構成成分である細胞壁を物理的に破壊することで殺菌効果を誘導し、薬剤耐性の有無にかかわらず抗体選択的に殺菌効果が得られる方法である。抗菌薬と異なる作用機序であり、薬剤耐性を誘導しにくいと考えられ、今後の耐性菌治療法開発に役立つと期待される。