Preclinical Study of a Fully Human Anti-PD-L1 Antibody as a Theranostic Agent for Cancer Immunotherapy

Recently, inhibiting the PD-1/PD-L1 checkpoint pathway utilizing anti-PD-1 or anti-PD-L1 antibodies has achieved great clinical success in cancer treatment. However, anti-PD-1 immunotherapy cannot be applied to all cancer patients, no more than 25% showed a positive response. Immunohistochemistry (IHC) is the gold standard to determine the PD-L1 expression level in malignant lesions, but a noninvasive imaging-meditated strategy is urgently required for clinical diagnosis to cover the shortcomings of invasive techniques. MX001, which is an anti-PD-L1 antibody, was labeled with Cu-64 (t1/2 = 12.7 h) and purified by PD-10 chromatography. Comprehensive studies including positron emission tomography (PET), ex vivo biodistribution, IHC, and immunotherapy have been performed in mice bearing MC38 (PD-L1 positive (+)) and 4T1 (PD-L1 negative (−)) xenografts. PET imaging of [18F]FDG was taken before and after therapy to monitor the therapeutic efficacy. [64Cu]Cu-NOTA-MX001 exhibited 2.3 ± 1.2, 5.6 ± 2.1, 5.6 ± 1.2,...