Biodistribution, dosimetry and imaging of 225Ac-DOTA-anti-PD-L1-BC in a murine immunocompetent transgenic breast cancer model

The recent development of immunomodulatory agents have brought immunotherapy up as a possible treatment against various types of cancers. This treatment approach is based on tumors avoiding immune system recognition by co-opting immune checkpoints intended to prevent autoimmunity. One of the immune checkpoint mediators is the Programmed Cell Death protein 1 (PD-1) receptor. PD-1 interacts with Programmed cell Death Ligand 1 (PD-L1). PD-L1 is expressed on a variety of tumor cells, tumor associated macrophages and other cells in the tumor microenvironment. Clinical trials of anti-PD-L1 antibodies have yielded promising results in patient populations, which have exhausted all other conventional therapeutic options. In addition a number of studies have shown the potential of combined immune checkpoint inhibition therapy and external beam radiotherapy. In this study we examine the feasibility of a 225Ac-labeled anti-PD-L1 antibody to deliver an alpha-particle emitting radionuclide in a murine immunocompetent transgenic breast cancer model.

JOSEFSSON Anders;  NEDROW Jessie;  PARK Sunju;  BAECK Tom;  HOBBS Robert F.;  BRAYTON Cory;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SGOUROS G.; 

2017-08-01

European Commission - Joint Research Centre

JRC106150

http://nucmed.w3.kanazawa-u.ac.jp/symposium/tat10/,    https://publications.jrc.ec.europa.eu/repository/handle/JRC106150,