Main Conference Day 3Thursday, 12 June 2025 - BST (British Summer Time, GMT+1)

T cell-engaging (TCE) multispecific antibodies demonstrate great clinical efficacy, though their molecular complexity is a challenge for drug manufacturability, developability, and obtaining desirable PK/PD properties. Here, we showcase the discovery and engineering of novel anti-CD3 heavy chain-only antibodies (HCAbs), which demonstrate T cell cytotoxicity comparable to clinically validated TCEs when paired with IgG or TCR modalities. This work introduces a flexible new tool for enabling this important class of biologics.

SAIL66, a next-generation tri-specific T-cell engager targeting CLDN6, CD3, and CD137, was developed using proprietary Dual-Ig® technology. Dual-Ig® enables unique ability to CD3 and CD137, but not simultaneously. SAIL66 demonstrates remarkable selectivity, avoiding cross-reactivity with related CLDN family. In vitro and in vivo studies reveal SAIL66's superior T cell activation and enhanced anti-tumor efficacy compared to conventional TCEs.

We present two case studies of how antibody-cytokine fusions can be engineered to modulate the tumor microenvironment (TME), inhibit tumor growth and affect the efficacy of cancer treatments. To attenuate the potency of cytokine antibody fusions, combination strategies using cytokine muteins in conjunction with functional masking units were employed. Localization and conditional activation of cytokine activity in the TME resulted in efficient tumor cell killing.