From Cold to Hot: Leveraging RNA Splicing Therapeutics to Unleash Antitumor Immunity for Breast Cancer Patients
Technical Report,15 Sep 2018,14 Sep 2019
BAYLOR COLL OF MEDICINE HOUSTON United States
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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.
- Medicine and Medical Research