Abstract:
:The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.
journal_name
Hum Vaccin Immunotherjournal_title
Human vaccines & immunotherapeuticsauthors
Kwok G,Yau TC,Chiu JW,Tse E,Kwong YLdoi
10.1080/21645515.2016.1199310subject
Has Abstractpub_date
2016-11-01 00:00:00pages
2777-2789issue
11eissn
2164-5515issn
2164-554Xjournal_volume
12pub_type
杂志文章,评审abstract::Dynamically changing social situation associated with migrations, increasing freedom rights, popularity of anti-vaccine movements and the resulting from that decrease in herd immunity, forces the medical society and the governments of various countries to reflect on the attitude toward vaccinations. Issues of freedoms...
journal_title:Human vaccines & immunotherapeutics
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journal_title:Human vaccines & immunotherapeutics
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doi:10.1080/21645515.2017.1403703
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pub_type: 杂志文章
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doi:10.4161/hv.22346
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pub_type: 杂志文章,评审
doi:10.4161/hv.24422
更新日期:2013-07-01 00:00:00
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doi:10.1080/21645515.2015.1067741
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journal_title:Human vaccines & immunotherapeutics
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doi:10.1080/21645515.2019.1593727
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doi:10.1080/21645515.2017.1420447
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doi:10.4161/hv.26422
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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