Abstract 6889: A gold-based antibody-drug conjugate with theranostic potential for synovial sarcoma

Abstract Synovial sarcoma is a rare form of cancer that occurs in the soft tissue adjacent to bones in adolescents and young adults. Although rare, it is ranked as the second most common malignant soft-tissue tumor in children. This cancer has a high metastatic rate with 50% of all cases exhibiting metastasis at the time of diagnosis. The first line of therapy for this cancer is surgery which is effective for the primary tumor, but in patients with metastatic disease, chemotherapy and radiation are the main therapeutic options. These therapies tend to have negative side effects due to their lack of specificity. Antibody-drug conjugates are a promising class of cancer therapeutics due to their specificity and reduced side effects. Of particular interest are gold-based antibody-drug conjugates due to their laser-induced temporal control and theranostic (diagnostic and therapeutic) capabilities. This work sought to develop a novel gold-based antibody-drug conjugate for synovial sarcoma with limited side effects. To accomplish this goal, a potential target receptor, Oncostatin M Receptor (OSMR), was identified. This receptor has been shown to be involved in cancer proliferation and migration when activated by its ligand, Oncostatin M(OSM). OSMR is highly expressed in various cancers including breast cancer. The mRNA and protein expression of OSMR in synovial sarcoma tumors was compared to normal tissues. An anti-OSMR antibody was conjugated to a fluorophore and the conjugate was injected into synovial sarcoma-bearing mice to assess the specificity and targeting ability of the antibody in vivo. Gold nanorods were then synthesized, characterized, and conjugated site-specifically to the anti-OSMR antibody. The over-expression of OSMR in synovial sarcoma tumors as compared to normal tissues was validated. An anti-OSMR antibody conjugated to a fluorophore targeted OSMR-expressing tumors and metastatic cells and discriminated between tumor and normal tissue in vivo. Gold nanorods were successfully synthesized and conjugated site-specifically to an anti-OSMR antibody. These findings suggest OSMR as a viable candidate for a targeted treatment of synovial sarcoma. They also suggest that an anti-OSMR conjugate can target both primary and metastatic tumors. The successful conjugation of gold nanorods to the anti-OSMR antibody opens the possibility of a theranostic approach to synovial sarcoma. Citation Format: Jeffrey Okojie, Bridger Kearns, Melanie l'anson-Holton, Andralyn McKell, Jared James Barrott. A gold-based antibody-drug conjugate with theranostic potential for synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6889.