PDL1-targeted vaccine exhibits potent antitumor activity by simultaneously blocking PD1/PDL1 pathway and activating PDL1-specific immune responses
| Autor: | Yanliang Kang, Wanli Zhang, Xingqun Gong, Wenbing Yao, Hongmei Chen, Xiaodao Song, Yi Xu, Hong Tian, Xiangdong Gao, Xuefei Xia, Yunyan Xu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Cellular immunity medicine.medical_treatment T cell Programmed Cell Death 1 Receptor Melanoma Experimental Mice Nude Apoptosis Cancer Vaccines B7-H1 Antigen Immune tolerance 03 medical and health sciences Mice 0302 clinical medicine Immune system Mice Inbred NOD medicine Tumor Cells Cultured Animals Humans Cell Proliferation Tumor microenvironment Mice Inbred BALB C business.industry Immunotherapy Xenograft Model Antitumor Assays Immune checkpoint Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Female Cancer vaccine business |
| Zdroj: | Cancer letters. 476 |
| ISSN: | 1872-7980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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