STING-Activating CAR-NK Cell Therapy for the Systemic Treatment of Rare Gynecological Cancers
Abstract
Uterine sarcomas are rare and lethal cancers with inadequate screening and treatment options and dismal clinical outcomes. These cancers also disproportionately impact service members, relative to the general population, adversely impacting mission readiness and highlighting the urgent need for curative therapies. Uterine sarcomas typically escape immune surveillance and are largely unresponsive to current immunotherapies that have revolutionized the standard of care for other tumor types. A central cause for the lack of efficacy of current immunotherapies is the immunosuppressive tumor microenvironment in these tumors, where there is limited infiltration and activation of effector cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells within the tumor core. Our long-term goal is to develop engineered NK cells designed to generate STING-activating cyclic dinucleotide alarm signals specifically in response to tumor-released surface antigens, thereby converting the immunologically cold microenvironment into an immunoreactive one that drives immune tumor rejection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2023
- Accession Number
- AD1229982
Entities
People
- Douglas E. Feldman
Organizations
- University of Southern California