Main Conference Day 3Wednesday, 17 December 2025 - PT (Pacific Time, GMT-08:00)

We will discuss the pros and cons of bispecific T-cell engagers (TCEs) relative to CAR-T cell therapies as well as protein-engineering strategies that can be employed to address limitations of TCEs for cancer therapy.

The use of T-cell engagers in solid tumors is currently limited by the availability of antigens that distinguish cancerous from healthy tissues. Using a lab-integrated, AI/ML-driven antibody engineering platform, we demonstrate that potent T-cell engagers can be rapidly generated against well-known solid-tumor targets, achieving robust tumor clearance without the typical on-target toxicities. We highlight case studies featuring both avidity-based and Boolean logic-controlled T-cell engager architectures across multiple solid malignancies.

Using an entirely original strategy, we have developed a novel platform that uses dual-binding antibodies to generate therapeutics with targeted, conditional activity only when bound to a selected marker. We are currently applying this Antibody Controlled Therapeutic technology to multiple targets, including PD1, LAG3, ATP, and LRRC15 and to multiple effectors including IL-2, IFN-a, IL-12 and TGFb inhibition.

While IL-2 has been shown to be key cytokine for the promotion of T-cell proliferation and effector function, its clinical use for cancer immunotherapy has been limited by severe toxicities. This talk describes the pre-clinical development of REGN10597, a PD-1 targeted receptor masked wild type IL-2 that demonstrates potent in vitro and in vivo activity when targeted to PD-1 expressing T cells but lowered systemic activity in the absence of targeting.

Targeted therapy with covalent inhibitors of oncoprotein KRAS(G12C) are initially effective but typically lack durability due to cancer cell resistance. MHC presentation of the covalently modified KRAS(G12C) peptides on the cell surface creates synthetic neoantigens that can be stabilized and targeted by antibodies across HLA restriction. Conversion to T-cell engagers affords a unique combination of targeted and immune therapy.