Toretsky, J. | bioRxiv Science

bioRxiv2023

An EWS::FLI1 monoclonal antibody with multimodal utility and specificity for FLI1

Ewing sarcoma (ES) is a rare tumor that affects children, adolescents, and young adults. This tumor has a high morbidity in all patients and for those who present with metastatic disease a high mortality. A canonical chromosomal translocation, either t(11;22)(q24;p12) or t(21;22)(q22;q12) leads to the fusion oncoproteins EWS::FLI1 or EWS::ERG in 95% of ES patients. We recognized a critical need for a stably sourced high affinity antibody that recognizes EWS::FLI1 with maximal specificity. We created and validated a hybridoma that produces a mouse derived monoclonal antibody that recognizes EWS::FLI1 in multiple molecular biology applications.

molecular biology↗

bioRxiv2020

Inhibiting DDX3X triggers tumor-intrinsic type I interferon response and enhances anti-tumor immunity

Accumulating evidence has shown that cellular double-stranded RNAs (dsRNAs) induce antiviral innate immune responses in human normal and malignant cancer cells. However, it is not fully understood how endogenous self dsRNA homeostasis is regulated in the cell. Here, we show that an RNA-binding protein, DEAD-box RNA helicase 3X (DDX3X), prevents the aberrant accumulation of cellular dsRNAs. Loss of DDX3X induces dsRNA sensor-mediated type I interferon signaling and innate immune response in breast cancer cells due to abnormal cytoplasmic accumulation of dsRNAs. Dual depletion of DDX3X and a dsRNA-editing protein, ADAR1 synergistically activates the cytosolic dsRNA pathway in breast cancer cell. Moreover, inhibiting DDX3X enhances the antitumor activity by increasing tumor intrinsic-type I interferon response, antigen presentation, and tumor-infiltration of cytotoxic T cells as well as dendritic cells in breast tumors, which may lead to the development of breast cancer therapy by targeting DDX3X in combination with immune checkpoint blockade.

cancer biology↗