Federal Grant Award Summary

The University of Texas Southwestern Medical Center received a $426,828 Project Grant from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) for research titled "Targeting Epigenetic Vulnerabilities in Osteosarcoma to Enhanced Immunotherapy." The award period runs from June 1, 2026, through May 31, 2028. This research focuses on developing enhanced immunotherapy approaches for osteosarcoma, the most common bone sarcoma in children, by addressing two primary obstacles: the immunosuppressive tumor microenvironment and secondary immune toxicity. The project will examine both tumor cell-intrinsic mechanisms (specifically epigenetic dysregulation that reduces Major Histocompatibility Complex Class I expression) and tumor cell-extrinsic mechanisms (including elevated expression of immune checkpoint molecules CD47 and PD-L1).

The research will deliver novel therapeutic approaches through two complementary strategies. First, the team will develop acid-resistant immunocytokines that simultaneously block CD47 and PD-L1 activities while activating Interleukin-2 signaling in tumor-infiltrating CD8 T cells to enhance antitumor efficacy with reduced systemic toxicity. Second, utilizing CRISPR epigenetic screening results, the investigators will target specific epigenetic modifiers to enhance tumor antigen presentation. The combination of these approaches is hypothesized to produce more robust systemic antitumor responses for improved osteosarcoma treatment outcomes. Research will be conducted at UT Southwestern's Dallas, Texas facility.