Core Insights - TuHURA Biosciences presented new scientific evidence at the 67th American Society of Hematology Annual Meeting, highlighting the role of Delta Opioid Receptor (DOR) in modulating the immunosuppressive capabilities of Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs) [1][2][3] Group 1: DOR and MDSCs - DOR is expressed on MDSCs, and its inhibition reduces their immune suppressing capabilities by downregulating multiple genes associated with immunosuppression [1][2] - Pharmacological antagonism of DOR has been shown to reverse T cell suppression, indicating that DOR may serve as a novel target for reprogramming MDSC-induced immunosuppression in the tumor microenvironment [2][4] Group 2: DOR and TAMs - DOR is also expressed on TAMs, and targeting DOR can potentially reverse TAM-mediated T cell suppression, which may help overcome resistance to checkpoint inhibitors and other cancer immunotherapies [1][3] - The study indicates that the tumor microenvironment induces DOR upregulation in TAMs compared to peripheral macrophages, suggesting a promising strategy for reprogramming these suppressive cells [3][4] Group 3: Company Developments - TuHURA has developed a library of highly selective DOR antagonists and is advancing its first-in-class immune-modulating bi-functional, bi-specific antibody drug conjugates (ADCs) [4][5] - The lead ADC candidate is expected to consist of a DOR inhibitor conjugated to a VISTA inhibiting antibody, aiming to alleviate the immunosuppressive tone of the tumor microenvironment and enhance T cell activity [4][5][6] Group 4: Clinical Trials and Future Directions - TuHURA has initiated a Phase 3 trial for its innate immune agonist, IFx-2.0, as an adjunctive therapy to Keytruda for advanced or metastatic Merkel Cell Carcinoma [6][7] - The company is also developing TBS-2025, a VISTA inhibiting mAb asset, which is moving into Phase 2 development for mutNPM1 r/r AML [7]