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Monoclonal and Polyclonal Antibodies Research / HER2/EGFR in Cancer Research · Journal article
Antibody Therapeutics · September 4, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical characterization of a novel tri-specific T-cell engager (tsTCE3) targeting CEACAM5, CDH17, and CD3 in colorectal cancer models. The molecule demonstrates moderate binding affinity, in vitro cytotoxicity, and superior tumor growth inhibition compared to bi-specific comparators in three subcutaneous xenograft models, with minimal cytokine release observed. No human clinical data are presented; this work represents early-stage development requiring further validation.
Preclinical in vitro and in vivo xenograft study. Colorectal cancer cell lines (HT55, SW403, LS174T) expressing variable levels of CEACAM5 and CDH17; human T cells from peripheral blood; NCG immunocompromised mice.. Intervention: CEACAM5 x CDH17 x CD3 tri-specific T-cell engager (tsTCE3). Compared with: Cibisatamab analogue, 2+1 CEACAM5 x CEACAM5 x CD3 bivalent bispecific TCE, and 2+1 CDH17 x CDH17 x CD3 biparatopic TCE.
tsTCE3 binding affinity: CEACAM5 Kd 51.0 nM (human) / 109 nM (cynomolgus), CDH17 Kd 42.8 nM (human) / 9.26 nM (cynomolgus), CD3ε Kd 51.9 nM (human) In HT55 tumor model (CEACAM5-high/CDH17-high), tsTCE3 more efficacious than cibisatamab analogue and 2+1 CEACAM5 x CEACAM5 x CD3 bispecific TCE In LS174T tumor model (CEACAM5-high/CDH17-low), tsTCE3 more potent than 2+1 CDH17 x CDH17 x CD3 biparatopic TCE
No human clinical trial data presented; efficacy and safety in patients remains unknown.
This preclinical work does not directly inform current clinical practice. If subsequent human trials demonstrate clinical efficacy and safety, the tri-specific format and favorable cytokine profile may offer advantages over existing bi-specific T-cell engagers, but clinical validation is required before any therapeutic recommendation can be made.
First-in-class tri-specific T-cell engager showing promising preclinical efficacy in xenograft models, but lacks human clinical data and relies on surrogate endpoints and animal studies.
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Quoted from the source exactly as published.
This preclinical work does not directly inform current clinical practice. If subsequent human trials demonstrate clinical efficacy and safety, the tri-specific format and favorable cytokine profile may offer advantages over existing bi-specific T-cell engagers, but clinical validation is required before any therapeutic recommendation can be made.
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Abstract Background CEACAM5 and CDH17 are highly co-expressed in certain solid tumors including colorectal cancer (CRC). Current single-target based immunotherapies, such as antibody-drug conjugates (ADC) and T cell engagers (TCE), have shown promising efficacy in clinical trials. In this study, we generated a novel tri-specific TCE (tsTCE) targeting CEACAM5, CDH17, and CD3, aiming to enhance tumor-targeting selectivity and therapeutic efficacy. Methods Various TCE molecule formats, including 1+1 monovalent (CEACAM5 or CDH17 x CD3), 2+1 bivalent or biparatopic (CEACAM5 x CEACAM5 x CD3, CDH17 x CDH17 x CD3) and 1+1+1 tsTCEs (CEACAM5 x CDH17 x CD3) were generated. A lead tsTCE molecule was selected and investigated by antigen binding affinity, cell binding, T-cell-dependent cellular cytotoxicity, and T-cell activation in vitro. In addition, its’ in vivo antitumor efficacy were evaluated in subcutaneous HT55, SW403, and LS174T tumor xenografts in NCG mice engrafted with human PBMCs. Results The CEACAM5 x CDH17 x CD3 tsTCE (tsTCE3) possesses a moderate binding affinity to human/cynomolgus CEACAM5 (Kd: 51.0 nM / 109 nM), CDH17 (Kd: 42.8 nM / 9.26 nM), and human CD3ε (Kd: 51.9 nM). The tsTCE3 effectively kills tumor cells with variable expression levels of CEACAM5 and/or CDH17 and induces significant tumor growth inhibition in multiple CDX models. In the CEACAM5-high / CDH17-high HT55 tumor model, tsTCE3 was more efficacious than cibisatamab analogue and a 2+1 CEACAM5 x CEACAM5 x CD3 bivalent bispecific TCE, whereas in the LS174T tumor model (CEACAM5-high / CDH17-low) tsTCE3 was more potent than a 2+1 CDH17 x CDH17 x CD3 biparatopic TCE molecule. Notably tsTCE3 elicited minimal cytokine release in HT55 xenograft model. Conclusions Our tsTCE3 exhibits potent in vitro tumor cell killing and superior in vivo efficacy with a favorable safety profile, supporting its potential as a promising therapeutic agent for the treatment of CEACAM5 / CDH17 positive solid tumors.
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