MP48-20 EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES (TIL) FROM PRIMARY BLADDER TUMORS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2017MP48-20 EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES (TIL) FROM PRIMARY BLADDER TUMORS Michael Poch, Maclean Hall, Krithika Kodumudi Kodumudi, Cortlin Croft, Mayer Fishman, John Mullinax, Amod Sarniak, James Mule, and Shari Pilon-Thomas Michael PochMichael Poch More articles by this author , Maclean HallMaclean Hall More articles by this author , Krithika Kodumudi KodumudiKrithika Kodumudi Kodumudi More articles by this author , Cortlin CroftCortlin Croft More articles by this author , Mayer FishmanMayer Fishman More articles by this author , John MullinaxJohn Mullinax More articles by this author , Amod SarniakAmod Sarniak More articles by this author , James MuleJames Mule More articles by this author , and Shari Pilon-ThomasShari Pilon-Thomas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1501AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with advanced bladder cancer have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. At our institution, adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has resulted in a durable median OS of 52 months in patients with metastatic melanoma. Immune-mediated anti-tumor responses have been previously shown in bladder cancer, therefore we investigated the phenotype and function of TIL expanded from bladder tumors to establish feasibility of ACT for the treatment of bladder cancer. METHODS Tumor specimens, including primary bladder tumors and lymph node metastases, were collected from 29 bladder cancer patients having standard of care tumor resection, who also had consented to an IRB-approved protocol for TIL generation. The tissue was minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. TIL were considered expanded if they propagated to fill =2 wells. The remaining tumor material was digested into a single cell suspension and frozen. TIL were phenotyped by flow cytometry and assessed for autologous tumor reactivity through co-culture with tumor digest and IFN-gamma ELISA. RESULTS Twenty-seven of 29 tumors were harvested from radical cystectomy patients. Urothelial cell bladder tumors were cultured from 23 patients, of whom 19 (83%) demonstrated TIL expansion. Among these were 9/12 with preceding chemotherapy and 10/11 which had been chemotherapy naive. Expanded TIL were predominantly CD3+ (median 63%, range 10-87%) with a median of 30% CD8+ T cells (range 5-70%). Eight of 15 tested samples (53%) contained TIL that secreted IFN-gamma in response to autologous tumor. Microbial contamination was observed in six specimens. All lymphatic (5/5 samples) tissue collected demonstrated TIL expansion. CONCLUSIONS The study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer. Human bladder cancer tissue can be used to expand tumor-specific TIL in vitro. TIL were also able to be expanded from patients that received chemotherapy prior to tumor resection. Future efforts will explore the ability to further expand bladder TIL cultures to clinically meaningful numbers to develop novel ACT strategies for patients with this diagnosis. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e645 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Michael Poch More articles by this author Maclean Hall More articles by this author Krithika Kodumudi Kodumudi More articles by this author Cortlin Croft More articles by this author Mayer Fishman More articles by this author John Mullinax More articles by this author Amod Sarniak More articles by this author James Mule More articles by this author Shari Pilon-Thomas More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...