Shanghai and Hong Kong, China, November 8, 2026
Antengene Corporation Limited has announced the presentation of promising preclinical research findings for its proprietary AnTenGager-D2 costimulatory T-cell engager (Cos-TCE) platform at the 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting. The research was selected among the conference’s TOP 150 abstracts and presented in a Rapid Oral Abstract Presentation, highlighting the potential of this next-generation immunotherapy technology for treating solid tumors. The platform is designed to improve the ability of T cells to recognize and destroy cancer cells by combining two complementary immune activation signals. The research presentation, titled A CD2-based costimulatory T cell engager platform integrating a novel CD3γε/δε-targeting antibody and steric-hindrance-based CD3 masking, explored the platform’s molecular design, functional activity, safety characteristics and potential therapeutic applications. Antengene also presented preclinical findings for ATG-109, an investigational KLK2×CD2×CD3 T-cell engager developed using the AnTenGager-D2 technology. The candidate demonstrated encouraging antitumor activity in laboratory experiments and a prostate cancer animal model. These findings represent an important development milestone for Antengene’s immunotherapy research and support further investigation of costimulatory T-cell engager technologies.
Dual Immune Activation Strategy Targets Solid Tumors
Traditional CD3-based T-cell engagers work by connecting T cells with tumor cells, encouraging immune cells to recognize and attack cancer. Although this approach has demonstrated therapeutic potential, its application in solid tumors remains challenging because of the immunosuppressive tumor microenvironment, T-cell exhaustion and insufficient costimulatory signals. To address these limitations, Antengene developed AnTenGager-D2, which incorporates a novel CD3-targeting antibody, an engineered CD2-binding component and steric-hindrance-based CD3 masking. The platform is designed to provide two complementary signals for T-cell activation. The first signal is delivered through CD3 engagement, while the second is provided through the CD2/CD58 costimulatory pathway. This mechanism aims to activate T cells conditionally when the engager is connected to tumor-associated antigens. Researchers also evaluated the specificity of the platform’s parental anti-CD3 antibodies by screening 6,108 full-length human proteins and 403 human heterodimers. The antibodies demonstrated selective recognition of CD3δ/CD3ε and CD3γ/CD3ε heterodimers. Laboratory testing also showed fast-on, fast-off binding kinetics and substantially lower cytokine release compared with benchmark CD3 antibody clones. These design characteristics may help improve immune activation while reducing unwanted inflammatory responses.
ATG-109 Shows Promising Preclinical Antitumor Activity
A major highlight of the research was the evaluation of ATG-109, a KLK2×CD2×CD3 costimulatory T-cell engager developed using the AnTenGager-D2 platform. The investigational candidate targets kallikrein-related peptidase 2 (KLK2), a protein associated with prostate cancer cells, while engaging CD2 and CD3 to promote targeted T-cell activity. In laboratory studies, ATG-109 demonstrated enhanced T-cell-dependent cellular cytotoxicity against KLK2-positive prostate cancer cells compared with a clinical benchmark. Importantly, researchers reported no nonspecific cytotoxicity against KLK2-negative Du145 cells. The candidate also showed reduced binding to CD3-positive Jurkat cells in the absence of KLK2-mediated crosslinking, supporting its intended antigen-dependent activation mechanism. Further experiments using a human peripheral blood mononuclear cell (PBMC)-reconstituted prostate cancer cell-derived xenograft model demonstrated potent in vivo antitumor activity. The researchers also reported favorable molecular stability characteristics, including a melting temperature above 68°C and good stability under accelerated testing conditions. In human FcRn mice, ATG-109 demonstrated a pharmacokinetic half-life of approximately 183.5 hours, providing encouraging early information about its drug-like properties.
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Antengene Plans Further Development of Next-Generation TCEs
The latest findings support Antengene’s continued development of next-generation T-cell engager therapies for solid tumors and hematological malignancies. The company intends to advance further preclinical studies of ATG-109 and continue evaluating the broader AnTenGager-D2 platform. Researchers also investigated different platform formats, with the F2 configuration demonstrating the largest observed safety window among the evaluated DLL3-targeting constructs. The platform showed limited antigen-independent T-cell activation and no observed T-cell-to-T-cell crosslinking in the reported experiments. These characteristics could be important for developing more selective immunotherapies with improved therapeutic potential. Antengene’s broader AnTenGager technology portfolio includes investigational programs targeting several cancer-associated proteins, including CDH6, ALPPL2, LY6G6D, GPRC5D and LILRB4. However, the reported AnTenGager-D2 and ATG-109 findings are preclinical and have not yet established safety or efficacy in human clinical trials. Further research will be necessary to assess their clinical potential. Overall, the SITC 2026 presentation highlights Antengene’s efforts to improve T-cell engager design and expand the possibilities of targeted immunotherapy for difficult-to-treat solid tumors.
Source: Antengene press release
