Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling
Abstract The novel antibody-based immunotherapy in oncology exploits the activation of immune system mediated by immunomodulatory antibodies specific for immune checkpoints. Among them, the programmed death ligand-1 (PD-L1) is of particular interest as it is expressed not only on T-cells, but also o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2019-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-49485-3 |
| _version_ | 1818998846818091008 |
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| author | Margherita Passariello Anna Morena D’Alise Annachiara Esposito Cinzia Vetrei Guendalina Froechlich Elisa Scarselli Alfredo Nicosia Claudia De Lorenzo |
| author_facet | Margherita Passariello Anna Morena D’Alise Annachiara Esposito Cinzia Vetrei Guendalina Froechlich Elisa Scarselli Alfredo Nicosia Claudia De Lorenzo |
| author_sort | Margherita Passariello |
| collection | DOAJ |
| description | Abstract The novel antibody-based immunotherapy in oncology exploits the activation of immune system mediated by immunomodulatory antibodies specific for immune checkpoints. Among them, the programmed death ligand-1 (PD-L1) is of particular interest as it is expressed not only on T-cells, but also on other immune cells and on a large variety of cancer cells, such as breast cancer cells, considering its high expression in both ErbB2-positive and Triple Negative Breast Cancers. We demonstrate here that PD-L1_1, a novel anti-PD-L1 T -cell stimulating antibody, inhibits PD-L1-tumor cell growth also by affecting the intracellular MAPK pathway and by activating caspase 3. Similar in vitro results were obtained for the first time here also with the clinically validated anti-PD-L1 mAb Atezolizumab and in vivo with another validated anti-mouse anti-PD-L1 mAb. Moreover, we found that two high affinity variants of PD-L1_1 inhibited tumor cell viability more efficiently than the parental PD-L1_1 by affecting the same MAPK pathways with a more potent effect. Altogether, these results shed light on the role of PD-L1 in cancer cells and suggest that PD-L1_1 and its high affinity variants could become powerful antitumor weapons to be used alone or in combination with other drugs such as the anti-ErbB2 cAb already successfully tested in in vitro combinatorial treatments. |
| first_indexed | 2024-12-20T22:08:01Z |
| format | Article |
| id | doaj.art-d9ecd4a1d8dd4bf3b9fda68c98a561a7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T22:08:01Z |
| publishDate | 2019-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d9ecd4a1d8dd4bf3b9fda68c98a561a72022-12-21T19:25:14ZengNature PortfolioScientific Reports2045-23222019-09-019111310.1038/s41598-019-49485-3Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular SignallingMargherita Passariello0Anna Morena D’Alise1Annachiara Esposito2Cinzia Vetrei3Guendalina Froechlich4Elisa Scarselli5Alfredo Nicosia6Claudia De Lorenzo7Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”Nouscom srlDepartment of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”Ceinge – Biotecnologie Avanzate s.c. a.r.l.Nouscom srlDepartment of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”Abstract The novel antibody-based immunotherapy in oncology exploits the activation of immune system mediated by immunomodulatory antibodies specific for immune checkpoints. Among them, the programmed death ligand-1 (PD-L1) is of particular interest as it is expressed not only on T-cells, but also on other immune cells and on a large variety of cancer cells, such as breast cancer cells, considering its high expression in both ErbB2-positive and Triple Negative Breast Cancers. We demonstrate here that PD-L1_1, a novel anti-PD-L1 T -cell stimulating antibody, inhibits PD-L1-tumor cell growth also by affecting the intracellular MAPK pathway and by activating caspase 3. Similar in vitro results were obtained for the first time here also with the clinically validated anti-PD-L1 mAb Atezolizumab and in vivo with another validated anti-mouse anti-PD-L1 mAb. Moreover, we found that two high affinity variants of PD-L1_1 inhibited tumor cell viability more efficiently than the parental PD-L1_1 by affecting the same MAPK pathways with a more potent effect. Altogether, these results shed light on the role of PD-L1 in cancer cells and suggest that PD-L1_1 and its high affinity variants could become powerful antitumor weapons to be used alone or in combination with other drugs such as the anti-ErbB2 cAb already successfully tested in in vitro combinatorial treatments.https://doi.org/10.1038/s41598-019-49485-3 |
| spellingShingle | Margherita Passariello Anna Morena D’Alise Annachiara Esposito Cinzia Vetrei Guendalina Froechlich Elisa Scarselli Alfredo Nicosia Claudia De Lorenzo Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling Scientific Reports |
| title | Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling |
| title_full | Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling |
| title_fullStr | Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling |
| title_full_unstemmed | Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling |
| title_short | Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling |
| title_sort | novel human anti pd l1 mabs inhibit immune independent tumor cell growth and pd l1 associated intracellular signalling |
| url | https://doi.org/10.1038/s41598-019-49485-3 |
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