T cell engagers (TCEs) show tremendous promise for treating solid tumors, yet progress remains constrained by the scarcity of targets that combine potency with safety. Cartography’s ATLAS and SUMMIT platforms integrate single-cell RNA sequencing to identify both single and paired targets with high tumor selectivity and broad patient coverage. Using these tools, we discovered and advanced CBI-1214, a TCE targeting a highly tumor-restricted colorectal cancer antigen that entered the clinic in early 2026, and are extending this framework to the discovery of multi-specific (AND-gated) TCEs that further enhance therapeutic index. Together, these efforts illustrate a unified strategy for precision TCE and multispecific antibody discovery.

MAIT cells are an abundant, tissue and tumor resident, potent cytotoxic T cell subset. MAIT engagers (bispecific BiXAb antibodies) induce efficient tumor cytotoxicity but, in contrast to CD3 engagers, do not cause cytokine release. MAIT engagers do not induce regulatory T cell activation and are thus not dampened by increased immune suppression in the tumor. The increased safety and activity, especially in T-reg-rich tumors, affords a large therapeutic window.

This presentation will describe the development of a first-in-class T cell engager designed to target the T cell receptor β chain as a novel entry point for treating solid tumors. It will outline the overarching concept, general engineering strategy, and supporting preclinical observations.

T cell engagers (TCEs) can redirect immune cells to eliminate solid tumors, but their therapeutic index is limited by the scarcity of truly tumor-specific antigens that remain expressed under immune pressure. Neoantigens from driver mutations are both tumor-exclusive and essential for survival. Clasp’s TCEs targeting p53 and KRas neoantigens demonstrate high selectivity and potent anti-tumor activity in preclinical models, offering a precision approach to immunotherapy.

EM1032 is a clinical stage first-in-class TCE targeting ALPP/G and CD3 that has shown potent anti-tumor activities in a number of solid tumor models, including ovarian cancer where ALPP/G is highly expressed. Additionally, EM1032 demonstrated potent redirected T-cell cytotoxicity against the KRAS.G12V mutated PAAD cell line. In vivo, EM1032 in combination with a pan-KRAS inhibitor showed potent tumor growth inhibition in a xenografted mice model. Post-treatment histopathological analysis revealed a marked increase in tumor-infiltrating lymphocytes (TILs) concomitant with a reduction in ALPP-positive tumor cells, suggesting an immune-mediated antitumor mechanism. Preclinical toxicology studies indicated EM1032 was well tolerated in non-human primates and data will be presented.

Ability Biotherapeutics developed AbiLeap, an AI-enabled platform that systematically designs conditionally active, logic-gated antibodies. Focusing on CD3 and select tumor antigens such as mesothelin, these molecules overcome key therapeutic limitations by activating only in the tumor microenvironment while remaining inert in normal tissue. We demonstrate how AbiLeap enables on-demand generation of large antibody sets meeting defined design criteria for the efficient creation of logic-gated immune engagers.

LabGenius Therapeutics’ platform leverages avidity-driven selectivity to overcome T cell engager (TCE) challenges, including on-target, off-tumor toxicity. We describe how the closed-loop integration of high-throughput experimentation with machine learning has facilitated the discovery and optimization of multispecifics for function and developability. We share in vitro data demonstrating selective tumor-cell killing, alongside in vivo data highlighting the efficacy and tolerability of our lead asset, a highly tumor-selective bispecific TCE.

Preclinical and clinical data support combinations of bispecific antibodies engaging distinct T cell signaling pathways. Co-localizing "signal 1" (TCR/CD3) and "signal 2" (costimulation) within the tumor microenvironment by combining CD3-engaging and costimulatory pathway-engaging bispecific antibodies drives superior anti-tumor responses. Integrating signal 3 (cytokine support) through targeted delivery of cytokine signaling also enables deeper and more durable anti-tumor responses.

NK cells can induce remissions in patients with refractory leukemia. However, they lack specificity. To make NK cells antigen specific, we developed a Trispecific Killer Engagers (TriKEs), that engages NK cells (camelid anti-CD16) and tumor antigen with IL-15 between them. The goal of this therapy is to create immune synapses in vivo to target and activate endogenous NK cells to optimally treat leukemia (anti-CD33) and solid tumors (B7H3).

Synaptimmune Therapeutics, in collaboration with Lyvgen Biopharma, is developing conditionally active costimulatory T cell engagers (TCE) for autoimmune diseases and solid tumors. Leveraging our proprietary conditionally active (hidden CD3 binder) and integrated costimulation TCE platform (TROY-Ig) we have developed more potent and safe conditionally active 4-1BB costimulatory CD19 x CD20 TCEs (SYN8034) for autoimmunity and conditionally active CD2 costimulatory DLL3 TCEs (SYN8463) for SLC solid-tumor clinical development.

Tumor heterogeneity limits the efficacy of T Cell Engagers in solid tumors. Stereo has developed a robust, target-agnostic platform to discover and optimize Trackers, soluble small format TCRs. Trackers exhibit target specificity and antibody-like developability, and can be easily reformatted into multispecific T Cell Engagers (TCE). Here we show the robust functional activity of Tracker TCEs, supporting this novel molecule's potential to overcome heterogeneity challenges in solid tumors.

Oncology has arguably the greatest potential to benefit from mRNA technology, as antibody-based immunotherapies, which can easily be encoded as mRNA, have revolutionized care for many cancer types. Despite recent advances, multiple myeloma (MM) remains a largely incurable malignancy where patients cycle through many therapies. We have developed dual targeting mRNA encoded T cell engagers for combination treatment of MM, to improve depth and durability of remission.