Abstract 3553: Bria-OTS+: A versatile therapeutic platform for inducing anti-cancer immunity

Abstract Background: Despite advances, achieving curative cancer therapies remains challenging due to the complex, multi-stage nature of the disease. Recently, therapeutic cancer vaccines have shown promising efficacy, driven by advances in immune profiling, antigen selection, immunotherapy combinations, mRNA technology, and delivery platforms. However, challenges persist, including identifying highly immunogenic tumor antigens, overcoming T-cell immune escape, and achieving scalable, cost-effective manufacturing. To address these, BriaCell is developing a gene-modified allogeneic tumor cell platform to stimulate both innate and adaptive immunity. This platform provides a broad range of tumor antigens and includes immune-stimulatory factors to induce a comprehensive immune response. Initial results with the SV-BR-1-GM (Bria-IMT) breast cancer cell line, expressing GM-CSF, have shown promise. Bria-OTS+ further enhances immune activation by expressing additional cytokines, co-stimulatory factors, and HLA alleles across tumor cells, offering a personalized, adaptable immunotherapy platform. Methods: Bria-OTS+ cell lines are derived from various cancer lines, including breast, prostate, lung, and melanoma. The cells are modified to express co-stimulatory molecules, cytokines and a range of HLA alleles through lentiviral transduction. To assess Bria-OTS+’s therapeutic potential, we developed an in vitro vaccination assay. Briefly, peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with Bria-OTS+ cells in a four-phase assay—priming, resting, boosting and effector phases—to evaluate immune activation, memory formation, exhaustion, and cytotoxicity. Results: Bria-OTS+ robustly activated innate and adaptive immune responses in vitro. Co-culture with PBMCs led to T and NK cell activation, marked by increased activation markers and cytokine production. The platform induced immune memory, with enhanced cytokine release, cytotoxicity and memory marker expression upon re-stimulation. Cytotoxicity assays confirmed effective tumor cell targeting, and blocking antibody studies identified key activation pathways. Conclusions: Bria-OTS+ is an adaptable cancer immunotherapy platform with strong clinical potential. It expresses a broad range of cancer antigens, including Tumor-Associated Antigens and Post-Translational Modifications, to stimulate robust immune responses. The platform activates both adaptive and innate immunity, overcoming immune escape by engaging NK cells in cases of HLA deletion. Bria-OTS+ is flexible, easily updated with new innovations, and suited for both personalized and ready-to-use applications. Its simplified administration and anticipated favorable side effect profile support broad clinical potential and patient tolerance. Citation Format: Miguel A. Lopez-Lago, Vikas Bhardwaj, Pravin Kesarwani, Xiaoyi Zheng, sagarika Pachhal, Patience Cournoo, Renee Cortez, George Woodfield, Charles Wiseman, William Williams. Bria-OTS+: A versatile therapeutic platform for inducing anti-cancer immunity [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 3553.