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Review
. 2020 Jul 7:11:1508.
doi: 10.3389/fimmu.2020.01508. eCollection 2020.

Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment-Current Progress, Strategy, and Future Perspective

Libin Guo  1 , Ran Wei  1 , Yao Lin  2 , Hang Fai Kwok  1
Affiliations
Review

Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment-Current Progress, Strategy, and Future Perspective

Libin Guo et al. Front Immunol. .

Abstract

Targeting PD-L1 and PD-1 interactions is a relatively new therapeutic strategy used to treat cancer. Inhibitors of PD-1/PD-L1 include peptides, small molecule chemical compounds, and antibodies. Several approved antibodies targeting PD-1 or PD-L1 have been patented with good curative effect in various cancer types in clinical practices. While the current antibody therapy is facing development bottleneck, some companies have tried to develop PD-L1 companion tests to select patients with better diagnosis potential. Meanwhile, many companies have recently synthesized small molecule inhibitors of PD-1/PD-L1 interactions and focused on searching for novel biomarker to predict the efficacy of anti-PD-1/PD-L1 drugs. This review summarized clinical studies and patent applications related to PD-1/PD-L1 targeted therapy and also discussed progress in inhibitors of PD-1/PD-L1.

Keywords: PD-1; PD-L1; clinical trial; immunotherapy; patent.

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Figures

Figure 1
Figure 1
PD-1/PD-L1 or PD-1/PD-L2 in the tumor microenvironment. PD-1 is expressed on T-cells and NK cells. PD-L1 is expressed in tumor cells, antigen presenting cells, cancer associated fibroblasts, and in several immune cells (myeloid cells, endothelial cells, M2 macrophages). The binding of PD-L1 or PD-L2 to PD-1 could inhibit the functioning of T-cells and NK cells. IFN-γ secreted by activated T-cells mediates the up-regulation of tumor PD-L1. The blockade of PD-1/PD-L1 or PD-1/PD-L2 interaction by PD-1 or PD-L1 inhibitors could restore T-cell or NK cell activation.
Figure 2
Figure 2
Numbers of international patent applications published per year containing the word “PD-1” or “PD-L1” in the title, claim, or abstract.
Figure 3
Figure 3
Clinical trials related to anti-PD-1/PD-L1 antibodies. (A) Numbers of clinical trials of anti-PD-1 antibodies. (B) Numbers of clinical trials of anti-PD-L1 antibodies. Antibodies that obtained approval for cancer therapy are indicated by an asterisk.
See this image and copyright information in PMC

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