Cited 29 times in
Promising preclinical platform for evaluation of immuno-oncology drugs using Hu-PBL-NSG lung cancer models
DC Field | Value | Language |
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dc.contributor.author | 조병철 | - |
dc.contributor.author | 표경호 | - |
dc.date.accessioned | 2019-02-14T01:58:36Z | - |
dc.date.available | 2019-02-14T01:58:36Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0169-5002 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/167322 | - |
dc.description.abstract | BACKGROUND: With the advance of immunotherapy, treatment of non-small-cell lung cancer (NSCLC) has revolutionized by having anti-PD-1 therapy in front-line setting. In this era of cancer immunotherapy, humanized mouse models which recapitulate human immune system, are needed for predicting immunotherapy response in patients. We established a Hu-PBL-NSG mouse model which can be used as a preclinical testing platform for assessing efficacy of different immunotherapeutic agents. MATERIALS AND METHODS: Hu-PBL-NSG mouse model was established by engrafting human peripheral blood mononuclear cells (PBMCs) into NOD/scid/IL-2Rγ-/- (NSG) mice. Cytokine array was performed to assess serological similarity between patient and the Hu-PBL-NSG mouse, and microscopic immune cell infiltration was observed in various organs mouse model. Human anti-PD-1 therapy was treated for assessing drug efficacy in patient-derived tumor. RESULTS: hCD3+hCD45+ T-cells and antigen presenting cells (dendritic cells, macrophages, and MDSC) increased in the serum of Hu-PBL-NSG mouse 24 h after the transfusion of human PBMCs, and CD3 + T cells were observed in lung, liver, kidney, spleen sections. Cytokine arrays of human and Hu-PBL-NSG mouse revealed high similarity of Th1, Th2, Th17-related cytokines. A tumor xenograft was engrafted from an EML4-ALK patient, and Hu-PBL-NSG mouse was sacrificed for histological analyses. hCD3+ T cells were infiltrated within the tumor, and CD11c + cells, which represent antigen-presenting capability, were seen in spleen, lung, liver and kidney. When anti-PD-1 Ab was treated intraperitoneally, xenograft tumor showed significant reduction in volume after day 6, and increased expression of immune response-related genes on microarray analysis in the tumor. Mostly IFN-gamma and its related gene sets were significantly changed (FDR < 0.25, GSEA). CONCLUSION: Hu-PBL-NSG mouse model which highly resembles human immune system was successfully established. This model could be a strong preclinical model for testing efficacy of immunotherapeutic agents, and also for pursuing novel immunotherapy treatment strategies in advanced NSCLC. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier Scientific Publishers | - |
dc.relation.isPartOf | LUNG CANCER | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Promising preclinical platform for evaluation of immuno-oncology drugs using Hu-PBL-NSG lung cancer models | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Kyoung Ho Pyo | - |
dc.contributor.googleauthor | Jae Hwan Kim | - |
dc.contributor.googleauthor | Ji-Min Lee | - |
dc.contributor.googleauthor | Sung Eun Kim | - |
dc.contributor.googleauthor | Jae Seok Cho | - |
dc.contributor.googleauthor | Sun Min Lim | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.identifier.doi | 10.1016/j.lungcan.2018.11.035 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A04809 | - |
dc.relation.journalcode | J02174 | - |
dc.identifier.eissn | 1872-8332 | - |
dc.identifier.pmid | 30642538 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0169500218306755 | - |
dc.subject.keyword | EML4-ALK | - |
dc.subject.keyword | Hu-PBL-NSG | - |
dc.subject.keyword | Humanized mouse | - |
dc.subject.keyword | Immunotherapy | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.contributor.affiliatedAuthor | 표경호 | - |
dc.citation.volume | 127 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 112 | - |
dc.citation.endPage | 121 | - |
dc.identifier.bibliographicCitation | LUNG CANCER, Vol.127(1) : 112-121, 2019 | - |
dc.identifier.rimsid | 61522 | - |
dc.type.rims | ART | - |
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