Near infrared photoimmunotherapy with an anti-mesothelin antibody

// Tadanobu Nagaya 1 , Yuko Nakamura 1 , Kazuhide Sato 1 , Yi-Fan Zhang 2 , Min Ni 2 , Peter L. Choyke 1 , Mitchell Ho 2 , Hisataka Kobayashi 1 1 Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA 2 Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA Correspondence to: Hisataka Kobayashi, e-mail: kobayash@mail.nih.gov Keywords: near infrared photoimmunotherapy, mesothelin, hYP218, humanized monoclonal antibodies, molecular imaging Received: February 05, 2016      Accepted: February 28, 2016      Published: March 10, 2016 ABSTRACT Near Infrared-Photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs an antibody-photon absorber conjugate (APC). When the APC attaches to its target cell and is exposed to NIR light, highly selective cell killing is observed. NIR-PIT has been demonstrated with a limited number of antibodies. Mesothelin is overexpressed in several malignancies and is emerging as a therapeutic target. A recently humanized antibody (hYP218) has been generated against mesothelin that demonstrates high affinity binding. Here, we describe the efficacy of NIR-PIT, using hYP218 as the antibody within the APC to target a mesothelin expressing A431/H9 cell. The hYP218 antibody was conjugated to a photo-absorber, IR700 and incubated with the cells. The hYP218-IR700 showed specific binding to cells and cell-specific killing was observed in vitro . After implanting A431/H9 cells in an athymic nude mouse, tumor-bearing mice were treated with the following regimen of NIR-PIT; 100 μg of hYP218-IR700 i.v., NIR light was administered at 50 J/cm 2 on day 1 after injection and 100 J/cm 2 of light on day 2 after injection. The hYP218-IR700 showed high tumor accumulation and a high tumor-background ratio (TBR). Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other control groups ( p < 0.001), and significantly prolonged survival ( p < 0.0001 vs other groups). Thus, the new anti-mesothelin antibody, hYP218, is suitable as an antibody-drug conjugate for NIR-PIT. Furthermore, NIR-PIT with hYP218-IR700 is a promising candidate for the treatment of mesothelin-expressing tumors that could be readily translated to humans.