PD49-10 EFFECT OF CYTOTOXIC T LYMPHOCYTE REGENERATED FROM IPS CELLS IN PRECLINICAL MODELS OF RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (PD49)1 Sep 2021PD49-10 EFFECT OF CYTOTOXIC T LYMPHOCYTE REGENERATED FROM IPS CELLS IN PRECLINICAL MODELS RENAL CELL CARCINOMA Soki Kashima, Takuya Maeda, Kyoko Masuda, Seiji Nagano, Takamitsu Inoue, Takashi Kobayashi, Koji Terada, Yasutoshi Agata, Kazuyuki Numakura, Mitsuru Saito, Shintaro Narita, Masaki Yasukawa, Osamu Ogawa, Hiroshi Kawamoto, and Tomonori Habuchi KashimaSoki Kashima More articles by this author , MaedaTakuya Maeda MasudaKyoko Masuda NaganoSeiji Nagano InoueTakamitsu Inoue KobayashiTakashi Kobayashi TeradaKoji Terada AgataYasutoshi Agata NumakuraKazuyuki Numakura SaitoMitsuru Saito NaritaShintaro Narita YasukawaMasaki Yasukawa OgawaOsamu Ogawa KawamotoHiroshi Kawamoto HabuchiTomonori View All Author Informationhttps://doi.org/10.1097/JU.0000000000002071.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since the checkpoint inhibitors are effective only in a small number patients often cause severe adverse events, we developed novel immunotherapeutic strategy using induced pluripotent stem cells (iPSCs). The advantage is that all regenerated inherit express same rearranged T-cell receptor (TCR) when cytotoxic lymphocytes (CTLs) from iPSCs originally derived an antigen-specific cell (T-iPSC). We assessed effect therapy preclinical models renal carcinoma (RCC) targeting WT1 antigen because highly expressed RCC. METHODS: Human RCC lines including TUHR10 (WT1+, HLA-A*24:02 (A24)+); A498 (WT1-, A24-); VMRC A24-) were used as vitro vivo target cells. For model, cell-line xenograft (CDX) was prepared inoculating luciferase gene-transferred under kidney capsule immunodeficient mice. Moreover, patient-derived (PDX) clear Each A24+WT1+ PDX A24+WT1- tumors subcutaneously inoculated into right left sides on back mouse. As effector for line experiments, WT1-specific CTLs expanded healthy donor with A24 reprogrammed iPSCs. T-iPSCs (WT1-CTLs). In allogeneic approach applied transducing HLA-haplotype homozygous TCR α/β genes (TCR-iPSCs). Furthermore, TCR-iPSCs (WT1-TCR-CTLs). RESULTS: vitro51Cr release cytotoxicity assay, activity WT1-CTLs significantly higher than or (p < 0.05 p 0.05, respectively). CDX mean tumor size smaller WT1-CTLs-injected group control 0.01). WT1-TCR-CTL specifically suppressed growth WT1+ but not WT1- 0.05). CONCLUSIONS: demonstrated T-iPSC method effectively inhibited model. addition, TCR-iPSC utilizing clinically applicable materials impaired Our may serve against Source Funding: This work supported JSPS KAKENHI Grant Number JP18J10676 (Grant-in-Aid Fellow); AMED JP19cm0106203, JP18im0210611, JP19cm0106364; Join Usage/Research Center program Institute Frontier Life Medical Sciences, Kyoto University, Japan; Kanae Foundation Promotion Science, Bristol Myers Squibb Company Education Grants 2016 27447015, Japanese branch at Japan © 2021 American Urological Association Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e849-e849 Advertisement Copyright Permissions© Inc.MetricsAuthor Information Expand Loading ...