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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Margherita Passariello, Anna Morena D’Alise, Annachiara Esposito, Cinzia Vetrei, Guendalina Froechlich, Elisa Scarselli, Alfredo Nicosia, Claudia De Lorenzo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9ecd4a1d8dd4bf3b9fda68c98a561a7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d9ecd4a1d8dd4bf3b9fda68c98a561a7
record_format	dspace
spelling	oai:doaj.org-article:d9ecd4a1d8dd4bf3b9fda68c98a561a72021-12-02T15:08:08ZNovel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling10.1038/s41598-019-49485-32045-2322https://doaj.org/article/d9ecd4a1d8dd4bf3b9fda68c98a561a72019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49485-3https://doaj.org/toc/2045-2322Abstract 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.Margherita PassarielloAnna Morena D’AliseAnnachiara EspositoCinzia VetreiGuendalina FroechlichElisa ScarselliAlfredo NicosiaClaudia De LorenzoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	novel human anti-pd-l1 mabs inhibit immune-independent tumor cell growth and pd-l1 associated intracellular signalling
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d9ecd4a1d8dd4bf3b9fda68c98a561a7
work_keys_str_mv	AT margheritapassariello novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT annamorenadalise novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT annachiaraesposito novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT cinziavetrei novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT guendalinafroechlich novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT elisascarselli novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT alfredonicosia novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling AT claudiadelorenzo novelhumanantipdl1mabsinhibitimmuneindependenttumorcellgrowthandpdl1associatedintracellularsignalling
_version_	1718388285355589632

Novel Human Anti-PD-L1 mAbs Inhibit Immune-Independent Tumor Cell Growth and PD-L1 Associated Intracellular Signalling

Ejemplares similares