Ultrasound-Guided Targeted STING Activation for Breast Cancer Immunotherapy
Abstract
Despite recent successes of cancer immunotherapy, only a fraction of patients with breast cancer benefit from such treatment. Therefore, there is an urgent and unmet need to develop more effective immunotherapy strategies for breast cancer patients. Purpose: Our proposal aims to develop a novel and translatable strategy using microbubble-assisted US activation (MUSIC) to enhance STING activation in antigen presenting cells (APCs) to treat highly aggressive breast cancers. Scope: We will first evaluate MUSIC's ability to activate STING in vivo and its antitumor effect against different subtypes of breast tumors. We will then determine whether MUSIC treatment can produce systemic antitumor immune responses as a monotherapy or in combination with an anti-PD-1 antibody against metastatic breast cancers. Results: We have shown that MUSIC treatment promotes the activation of cGAS-STING pathway in APCs and enhance type I interferon responses by bone-marrow derived APCs as well as tumor associated macrophages (TAMs) from both mouse and human. We have also found that MUSIC inhibited tumor growth in syngeneic breast cancer models and its effect is dependent on host STING signaling. Significance: These results confirm our hypothesis that MUSIC can activate STING in APCs and promote antitumor immune responses against breast cancer in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1190610
Entities
People
- Wen Jiang
Organizations
- The University of Texas MD Anderson Cancer Center