Pd17-10 discovery of a novel monoclonal pd-l1 antibody h1a that promotes t-cell mediated tumor killing activity in renal cell carcinoma

You have accessJournal of UrologyCME1 Apr 2023PD17-10 DISCOVERY OF A NOVEL MONOCLONAL PD-L1 ANTIBODY H1A THAT PROMOTES T-CELL MEDIATED TUMOR KILLING ACTIVITY IN RENAL CELL CARCINOMA Reza Nabavizadeh, Rodrigo Rodrigues Pessoa, Zesheng An, Joanina Gicobi, Susan Harrington, Henan Zhang, Tianxiao Xu, Jacob Hirdler, Christine Lohse, Bradley Leibovich, Haidong Dong, and Fabrice Lucien Reza NabavizadehReza Nabavizadeh More articles by this author , Rodrigo Rodrigues PessoaRodrigo Rodrigues Pessoa More articles by this author , Zesheng AnZesheng An More articles by this author , Joanina GicobiJoanina Gicobi More articles by this author , Susan HarringtonSusan Harrington More articles by this author , Henan ZhangHenan Zhang More articles by this author , Tianxiao XuTianxiao Xu More articles by this author , Jacob HirdlerJacob Hirdler More articles by this author , Christine LohseChristine Lohse More articles by this author , Bradley LeibovichBradley Leibovich More articles by this author , Haidong DongHaidong Dong More articles by this author , and Fabrice LucienFabrice Lucien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint inhibitors (ICI) have shown conflicting outcomes in the adjuvant setting for high-risk clear cell renal cell carcinoma (ccRCC) patients. There is an unmet need to identify patients who would benefit from ICI treatment and to develop new therapies for those who progress on current anti PD1/PD-L1 treatments. Our group has recently created a novel monoclonal antibody (H1A) that induces PD-L1 destabilization at the cell surface resulting in its degradation. In this study, we evaluated the T-cell killing rate in response to current FDA approved treatments as well as H1A. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 13 subjects 3 months after nephrectomy for ccRCC. For treatment with ICI, antibodies were added at the time of activation with soluble anti-CD3 and at 20 μg/ml concentration. Human 786-O ccRCC cells was used as target cells and killing rates were measured by calcein release assay. Paired ANOVA test was used to compare efficacy of ICI. RESULTS: The median increase in T-cell killing rate for pembrolizumab, nivolumab and atezolizumab were 37.8% (range 17.4%-57.7%), 36.6% (range 6 22.7%-65.4%) and 29.9% (range 10%-52.5%), respectively. Individual response to immune checkpoint inhibitors was heterogeneous with some patients showing stronger response with nivolumab (n=9) while others had better killing activity with pembrolizumab (n=3) and one patient with no difference between different treatments. No best response was observed with atezolizumab across all patients. Median killing rate for H1A was 41.7% (range 25%-71.2%). Overall, median killing rate was significantly higher with H1A compared to the pembrolizumab (p=0.0003) and nivolumab (p=0.003) (Figure 1). In terms of individual response, all H1A-treated patients showed improved tumor cell killing efficiency compared to other treatment groups. CONCLUSIONS: In this proof-of-concept, we showed differential T-cell cytotoxic activity in response to various FDA-approved ICI. Additionally, we demonstrated the therapeutic value of a newly developed PD-L1 monoclonal antibody that induces stronger cytotoxic tumor cell killing from ccRCC patient-derived CD8 T cells compared to other ICI. Source of Funding: This work was supported by NIH R01CA256927 (HD) and R01AI095239 (HD) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e499 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Reza Nabavizadeh More articles by this author Rodrigo Rodrigues Pessoa More articles by this author Zesheng An More articles by this author Joanina Gicobi More articles by this author Susan Harrington More articles by this author Henan Zhang More articles by this author Tianxiao Xu More articles by this author Jacob Hirdler More articles by this author Christine Lohse More articles by this author Bradley Leibovich More articles by this author Haidong Dong More articles by this author Fabrice Lucien More articles by this author Expand All Advertisement PDF downloadLoading ...