Main Conference Day 2Tuesday, 15 December 2026 - PT (Pacific Time, GMT-08:00)

Despite recent approvals of immunotherapy agents like ADCs and checkpoint inhibitors, achieving durable responses in ovarian cancer remains a critical unmet need. We present a rational combination strategy using CD3- and CD28-based bispecific T cell engagers to deliver both Signal 1 and Signal 2 to potentially overcome the immunosuppressive tumor microenvironment and improve efficacy and durability of response, particularly in platinum-resistant disease.

We identified Preferentially Expressed Antigen in Melanoma (PRAME), an intracellular cancer testis antigen (CTA), as a highly tumor selective antigen and identify a peptide, PRAME425, that is presented by major histocompatibility complex I (MHCI) as an attractive solid tumor TCE target. We describe the discovery of highly selective anti-PRAME425 pMHC antibodies that bind specifically to PRAME425 pMHC. By formatting these novel antibodies into TCEs, we demonstrate PRAME425 pMHC-specific killing of tumor cells.

Emerging clinical validation of co-stimulatory immunotherapies has highlighted their potential to enhance anti-tumor immune responses. Here, we present a next-generation EVOLVE T cell engager platform integrating CD2 co-stimulation with dual-antigen tumor targeting to enhance tumor selectivity and T-cell activation. This approach enables selective tumor-directed CD2 co-stimulation while reducing single-antigen dependence, with the potential to broaden patient coverage and improve the efficacy of T cell engagers.

Macrophages are critical effectors of antibody therapies for lymphoma, but the best targets to engage their function remain unknown. We developed a high-throughput strategy to engineer libraries of bispecific antibodies, and we screened the resulting therapeutic candidates for the ability to stimulate macrophage-mediated cytotoxicity. A bispecific comprising a SIRPα decoy domain and a CD38-targeting arm exhibited maximal efficacy with reduced risk of toxicity. Our approach can be applied more broadly to leverage anti-tumor responses by macrophages or other immune cells.

T cell engaging multi-specific antibodies are increasingly capable of safely delivering meaningful responses for patients with diverse disease states, but the best outcomes occur when TCEs are specifically directed to diseased cells and away from normal cells. Machine learning-guided design and optimization of antibody structure, affinity, and developability can greatly improve therapeutic activity and safety through AND, OR, and NOT logic, enabling the next generation of off-the-shelf therapeutics.

We engineered a novel class of TCEs utilizing a highly sensitive, near-neutral pH-gating mechanism. By precisely tuning the molecular switches of the engager, we achieved full, uncompromised cytotoxic potency at a threshold as high as pH 7.2, paired with a massive 100- to 1000-fold functional attenuation at healthy tissue pH (7.3–7.5). This sharp dynamic range ensures a virtually clean baseline with zero systemic inflammation, a safety profile that remains resilient even in the presence of highly concentrated circulating tumor cells (CTCs). We present preclinical data demonstrating how this precise engineering strategy effectively decouples safety from efficacy, providing a robust blueprint for translating solid tumor cell engagers into the clinic with an unprecedented therapeutic index.