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IMMU-68. SINGLE-CELL PROTEOMIC ANALYSIS OF IMMUNE CELL RESPONSE TO CHECKPOINT BLOCKADE USING 30-PARAMETER FLOW CYTOMETRY

  • Amber Giles
  • , Leonard Nettey
  • , Thomas Liechti
  • , Margaret Beddall
  • , Elizabeth Vera
  • , Deric Park
  • , Jing Wu
  • , Brett Theeler
  • , Christine Siegel
  • , Lisa Boris
  • , Nancy Garren
  • , Christine Bryla
  • , Ann McCoy
  • , Edjah Nduom
  • , Kareem Zaghloul
  • , Terri Armstrong
  • , Mario Roederer
  • , Mark Gilbert

Research output: Contribution to journalArticlepeer-review

Abstract

s vi137 NEURO-ONCOLOGY • NOVEMBER 2018 suppress immunity, but rather, heightened interferon-(IFN)-γ reactivity. Addition of ICIs (to animals primed with RNA-NPs) augmented periph-eral/intratumoral PD-1+CD8+ cells and mediated synergistic anti-tumor efficacy in settings where ICIs alone did not confer therapeutic benefit. These synergistic effects were mediated by type-I-interferon released from PD-L1+ plasmacytoid dendritic-cells. In translational studies, personal-ized mRNA-NPs (from whole tumor-transcriptome) were safe and active in a client-owned canine with a spontaneous malignant glioma. In this patient, RNA-NPs elicited robust immunologic activity with increased percentages of activated PD-L1+ APCs and IFNγ+CD8+ cells. CONCLUSION: RNA-NPs elicit widespread immune activation concomitant with inducible PD-L1 expression on intratumoral APCs that can be therapeutically exploited. Since RNA-NPs bypass cost/complexity of cellular thera-peutics, are amenable to central distribution, and can be made within days of tumor resection, these formulations can be expeditiously translated as biomodulators of GBM immunogenicity.
Original languageAmerican English
Pages (from-to)vi137-vi137
JournalNeuro-Oncology
Volume20
Issue numbersuppl_6
DOIs
StatePublished - May 2018

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