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PDL1-targeted vaccine exhibits potent antitumor activity by simultaneously blocking PD1/PDL1 pathway and activating PDL1-specific immune responses.
- Source :
-
Cancer letters [Cancer Lett] 2020 Apr 28; Vol. 476, pp. 170-182. Date of Electronic Publication: 2020 Feb 21. - Publication Year :
- 2020
-
Abstract
- Despite the clinical success of immune checkpoint blockade, only a subset of people exhibits durable responses, suggesting that an alternative immunotherapeutic strategy is required. This paper reported a two-in-one cancer vaccine that targets programmed death ligand 1 (PDL1) that blocks the PD1/PDL1 pathway and also activates antitumor immune response. The PDL1- NitraTh vaccine, which consists of the extracellular domain of PDL1 and nitrated T cell epitope, effectively broke the immune tolerance of PDL1 and elicited PDL1-specific humoral and cellular immunity. The treatment of PDL1-NitraTh exhibited potent antitumor activity. Moreover, immunization of PDL1 vaccine increased the infiltration of tumor lymphocytes and decreased the proportion of Treg cells in tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. The upregulation of PDL1 in tumor tissues was induced by PDL1-NitraTh vaccine but not in spleen and lymphomas. This upregulation of PDL1 is beneficial to the antitumor activity of PDL1-specific humoral and cellular immunity induced by PDL1-NitraTh. In summary, PDL1-targeted vaccine exhibits potent antitumor activity and may provide an alternative immunotherapy strategy for patients who are not sensitive to PDL1 antibody drugs.<br />Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclosure.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Apoptosis
B7-H1 Antigen immunology
Cancer Vaccines immunology
Cell Proliferation
Colonic Neoplasms immunology
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Female
Humans
Melanoma, Experimental immunology
Melanoma, Experimental metabolism
Melanoma, Experimental pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Nude
Programmed Cell Death 1 Receptor immunology
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
B7-H1 Antigen antagonists & inhibitors
Cancer Vaccines administration & dosage
Colonic Neoplasms drug therapy
Melanoma, Experimental drug therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 476
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 32092355
- Full Text :
- https://doi.org/10.1016/j.canlet.2020.02.024