Antengene Corporation Limited announced that it presented the latest preclinical results of its novel costimulatory T cell engager (Cos-TCE) platform AnTenGager-D2 in a Rapid Oral Abstract Presentation at the 2026 Society for Immunotherapy of Cancer Annual Meeting (SITC 2026). The study was selected as a TOP150 abstract by the conference.

Presentation Details

The presentation was titled "A CD2-based costimulatory T cell engager platform integrating a novel CD3γε/δε-targeting antibody and steric-hindrance-based CD3 masking," with poster number #896.

Study Rationale

According to the company, CD3-based T cell engagers (TCEs) have shown promising therapeutic efficacy in the treatment of hematological malignancies. However, clinical progress in solid tumors has been slow, largely owing to tumor microenvironmental factors such as the induction of T cell exhaustion and the potential of CD3-bispecifics mediated T cell anergy and dysfunction in the absence of adequate co-stimulation.

The CD2/CD58 axis serves as a pivotal bifunctional regulator, mediating both adhesion and co-stimulation during human T cell activation. In this study, Antengene developed the AnTenGager-D2 platform integrating a novel CD3γε/δε-targeting antibody, steric-hindrance-based CD3 masking, and an engineered CD2-binder. According to the company, this enables conditional T cell activation via CD3 (signal 1) and CD2 (signal 2) stimulation upon TAA crosslinking, providing enhanced anti-tumor activity and a wider therapeutic index.

ATG-109 (KLK2×CD2×CD3 AnTenGager-D2 TCE) is a candidate molecule developed based on the AnTenGager-D2 platform. In this study, Antengene evaluated its in vitro anti-tumor activity, thermostability, pharmacokinetic profile, and in vivo anti-tumor efficacy in a prostate cancer cell derived xenograft model.

Reported Results

  • Parental anti-CD3 mAbs characterization: By screening 6108 full-length human proteins and further 403 human heterodimers using Retrogenix's Cell Microarray Technology, the AnTenGager parental anti-CD3 mAb showed high specificity of CD3δ+CD3ε, CD3γ+CD3ε heterodimer. AnTenGager-D2 parental anti-CD3 mAbs (ATG-CD3) demonstrated “fast-on-fast-off” binding kinetics in SPR assay. ATG-CD3 mAbs induced substantially lower cytokine release than benchmark CD3 clones.
  • Engineered CD58 IgV proteins: These exhibited superior thermostability and enhanced TDCC activity. CD58 integrated DLL3 AnTenGagers showed enhanced T cell dependent cytotoxicity against DLL3 positive tumor cell (NCI-H524), with an IC50 value of single-digit picomoles.
  • Safety window: The AnTenGager-D2 platform expands the safety window of co-stimulatory TCEs via appropriate structural integration of engineered CD58v protein. The platform displays limited antigen-independent T cell activation and no T cell-T cell crosslinking. Among DLL3-targeting AnTenGager-D2 TCEs, Format F2 demonstrated the largest safety window.
  • ATG-109 efficacy and cytokine release: ATG-109 showed lower binding affinity to CD3+ Jurkat cells in the absence of KLK2 crosslinking. ATG-109 demonstrated enhanced TDCC against KLK2 positive tumor cell (VCaP) compared to benchmark and showed no non-specific cytotoxicity against KLK2-negative cells (Du145).
  • In vivo efficacy: ATG-109 demonstrated potent in vivo efficacy in human PBMC re-established prostate cancer cell derived xenograft model.
  • Stability and pharmacokinetics: ATG-109 demonstrated good thermostability and exhibits good PK profile in hFcRn mice with T1/2 of ~183.5h. ATG-109 demonstrated a melting temperature (Tm) of >68 ℃ and showed good stability at 10 mg/ml evaluated by SEC-HPLC (40 ℃ for 4 weeks).

Company Conclusion

Antengene states that AnTenGager-D2 is a proprietary platform developed by the company for developing next-generation co-stimulatory TCEs with enhanced efficacy and safety. ATG-109, a KLK2-targeting AnTenGager-D2 TCE, showed superior preclinical efficacy compared to a clinical benchmark. The company said it will further advance these preclinical studies.

About Antengene

Antengene Corporation Limited (SEHK: 6996.HK) describes itself as a global, R&D-driven, commercial-stage biotech company focused on developing first-in-class/best-in-class therapeutics for diseases with significant unmet medical needs. Its pipeline spans from preclinical to commercial stages, with key investigational candidates including ATG-022 (CLDN18.2 ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 x 4-1BB bispecific antibody), ATG-125 (B7-H3 × PD-L1 bispecific ADC), ATG-207 (αCD3-TGF-β bifunctional fusion protein), as well as T cell engager (TCE) programs developed using Antengene's proprietary AnTenGager platform.

AnTenGager is described by the company as its proprietary TCE 2.0 platform, featuring “2+1” bivalent binding for low expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform's broad applicability across autoimmune diseases, solid tumors and hematological malignancies, with programs targeting CD19 x CD3 (ATG-201 for B cell-related autoimmune diseases; partnered with UCB), CDH6 x CD3 (ATG-106 for ovarian cancer and kidney cancer; partnered with K2 Therapeutics established by MPM BioImpact), ALPPL2 x CD3 (ATG-112 for gynecological tumors, digestive system malignancies, bladder cancer and NSCLC), LY6G6D x CD3 (ATG-110 for microsatellite-stable colorectal cancer), GPRC5D x CD3 (ATG-021 for multiple myeloma), LILRB4 x CD3 (ATG-102 for acute myeloid leukemia and chronic myelomonocytic leukemia) and FLT3 x CD3 (ATG-107 for acute myeloid leukemia).

Antengene states that to date it has obtained 35 investigational new drug (IND) approvals in the U.S. and Asia, and obtained new drug application (NDA) approvals in 10 Asia Pacific markets. Its lead commercial asset, XPOVIO (selinexor), is approved in the Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia, and has been included in the national insurance schemes in five of these markets (Mainland of China, Taiwan China, Australia, South Korea and Singapore).