Show simple item record

dc.contributor.authorSuarez, Eloah Rabelloen_US
dc.contributor.authorChang, De-Kuanen_US
dc.contributor.authorSun, Jiusongen_US
dc.contributor.authorSui, Jianhuaen_US
dc.contributor.authorFreeman, Gordon J.en_US
dc.contributor.authorSignoretti, Sabinaen_US
dc.contributor.authorZhu, Quanen_US
dc.contributor.authorMarasco, Wayne A.en_US
dc.date.accessioned2016-11-18T20:46:41Z
dc.date.issued2016en_US
dc.identifier.citationSuarez, Eloah Rabello, De-Kuan Chang, Jiusong Sun, Jianhua Sui, Gordon J. Freeman, Sabina Signoretti, Quan Zhu, and Wayne A. Marasco. 2016. “Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model.” Oncotarget 7 (23): 34341-34355. doi:10.18632/oncotarget.9114. http://dx.doi.org/10.18632/oncotarget.9114.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29408263
dc.description.abstractAdvances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.isversionofdoi:10.18632/oncotarget.9114en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085160/pdf/en
dash.licenseLAAen_US
dc.subjectimmune checkpoint inhibitoren
dc.subjectT cell exhaustionen
dc.subjectchimeric antigen receptoren
dc.subjectcarbonic anhydrase IXen
dc.subjectinterleukin-21en
dc.titleChimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse modelen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorSun, Jiusongen_US
dc.date.available2016-11-18T20:46:41Z
dc.identifier.doi10.18632/oncotarget.9114*
dash.contributor.affiliatedMarasco, Wayne
dash.contributor.affiliatedZhu, Quan
dash.contributor.affiliatedSun, Jiusong
dash.contributor.affiliatedFreeman, Gordon
dash.contributor.affiliatedSignoretti, Sabina


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record