Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer

被引:140
作者
Josefsson, Anders [1 ]
Nedrow, Jessie R. [1 ]
Park, Sunju [1 ]
Banerjee, Sangeeta Ray [1 ]
Rittenbach, Andrew [1 ]
Jammes, Fabien [1 ]
Tsui, Benjamin [1 ]
Sgouros, George [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA
关键词
ANTI-PD-L1; ANTIBODY; TRANSGENIC MICE; EXPRESSION; CELL; BLOCKADE; IMMUNOTHERAPY; CARCINOMA; B7-H1; RADIOIMMUNOTHERAPY; HER-2/NEU;
D O I
10.1158/0008-5472.CAN-15-2141
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radionuclide Indium-111 (In-111) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of In-111-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Coinjection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of In-111-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of In-111 -DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. (C) 2015 AACR.
引用
收藏
页码:472 / 479
页数:8
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