A High Throughput Assay for the Detection of Stimulator of Interferon Genes (STING) Agonists

Author(s)

Michael J. Ingling, Rowan University

Date Approved

7-2019

Document Type

Thesis

Degree Name

Master of Science in Molecular Pathology and Immunology

Department

Molecular Biology

College

Graduate School of Biomedical Sciences

Sponsor

Venenum Biodesign/Genesis Biotechnology Group

First Advisor

Salvatore Caradonna, PhD

Committee Member 1

Michael McQueney, PhD

Committee Member 2

Grant Gallagher, PhD

Subject(s)

Tumor Escape, CD8-Positive T-Lymphocytes, Neoplasms, Medical Oncology

Disciplines

Cancer Biology | Immunopathology | Laboratory and Basic Science Research | Medicine and Health Sciences | Molecular Biology | Neoplasms | Pathogenic Microbiology

Abstract

The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. Activation of STING has been shown to induce profound CD8 T cell-led immune reaction against immunologically suppressed tumors, as well as a memory response upon rechallenge and abscopal response. Most importantly, its simplistic method of activation (intratumoral administration of CDN, with current research formulations exploring the IV route) has scientists clamoring for a CDN mimetic or molecule that likewise activates STING. Currently, numerous pharmaceutical companies have synthesized STING agonists, with some deviating from the canonical CDN formulation. These non-CDN molecules represent the next generation of STING agonists. This thesis set out to develop an efficient screen to discover next generation STING agonists within a commercial compound deck.

Recommended Citation

Ingling, Michael J., "A High Throughput Assay for the Detection of Stimulator of Interferon Genes (STING) Agonists" (2019). Graduate School of Biomedical Sciences Theses and Dissertations. 17.
https://rdw.rowan.edu/gsbs_etd/17