From Cold to Hot: Leveraging RNA Splicing Therapeutics to Unleash Antitumor Immunity for Breast Cancer Patients

Abstract

Although immune checkpoint blockade therapy (ICBT) emerged as an effective treatment on a subset of breast cancer patients, it remains a daunting challenge to make more patients respond. Our preliminary studies suggest that inhibition of splicing, a process to join the protein-coding parts of RNAs during gene expression, leads to immunostimulatory responses in triple negative breast cancers (TNBCs). We hypothesized that splicing inhibition accumulates mis-spliced RNAs, which may activate innate immune responses and lead to expression of neoantigens. In this application, we aim to test this hypothesis and examine if a clinically available splicing inhibitor can synergize with ICBT in immunocompetent models. We will also elucidate specific immune cells that may mediate such synergy.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2019
Accession Number
AD1089960

Entities

People

  • Xiang Zhang

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Blood
  • Breast Cancer
  • Cancer
  • Cells
  • Chemistry
  • Culture Techniques
  • Data Science
  • Gene Expression
  • Immune System
  • Immunity
  • Information Science
  • Lymphocytes
  • Myeloid Cells
  • Neoplasms
  • Spreadsheet Software
  • Statistical Analysis
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).
  • Systems Analysis and Design