ADCE-T02: A Next-generation Antibody–Drug Conjugate Targeting Tissue Factor Demonstrates Superior Preclinical Efficacy and Tolerability
- 1Adcendo Aps, Frederiksberg, Denmark.
- 2Multitude Therapeutics, Shanghai, China.
- 3Multitude Therapeutics, Redwood City, California.
Abstract
Tissue factor (TF) protein is involved in activating the extrinsic blood coagulation cascade. TF expression is normally anatomically limited to the perivascular space, but TF is overexpressed in many malignancies, including pancreatic, cervical, prostate, and head and neck cancers, which makes TF an ideal antibody–drug conjugate (ADC) target. The TF-ADC tisotumab vedotin is approved for cervical cancer treatment but induces substantial side effects including ocular toxicities, peripheral neuropathy, and bleeding, limiting its further clinical development and warranting optimized ADC design to improve the therapeutic window. ADCE-T02 is a novel TF-ADC comprising the monoclonal antibody Ab-T02 conjugated via a self-immolative linker to the topoisomerase 1 inhibitor exatecan at an average drug-to-antibody ratio of 4.5. In contrast to tisotumab, Ab-T02 does not inhibit coagulation factor X activation. ADCE-T02 binds TF with high affinity inducing ADC internalization, exatecan release, cancer cell death, and bystander cytotoxicity in vitro. In vivo, ADCE-T02 is highly efficacious across a range of cell line–derived and patient-derived xenograft models including hard-to-treat models with large tumors, resistance to standard of care, low and/or heterogeneous expression of TF, and multidrug resistance. Importantly, ADCE-T02 demonstrates favorable pharmacokinetic properties and is well tolerated in nonhuman primates and in contrast to tisotumab vedotin and other auristatin-based ADCs shows no evidence of ocular, skin, and lung toxicities; peripheral nerve damage; or bleeding. In summary, ADCE-T02 constitutes a novel TF-ADC with a much improved preclinical therapeutic window. Phase I clinical development of ADCE-T02 in patients with advanced solid tumors is ongoing (ClinicalTrials ID: NCT06597721).
Related
- 883 A novel CDH17/HER3 bispecific ADC demonstrates superior preclinical efficacy in colorectal cancer
- 618 A novel preclinical mouse model to investigate IL-18-targeting therapies
- Calreticulin-targeting L-asparaginase-flagellin conjugate enhances Salmonella-mediated antitumor efficacy
- Computational modeling and preclinical evaluation support targeting somatic instability for Huntington’s disease treatment
- Targeting IL-2 to inflamed tissues via oxidation-specific epitopes enables third-generation bispecific IL-2 therapeutics
BibTeX
@article{poulsen2026adcet02,
title = {{ADCE-T02: A Next-generation Antibody–Drug Conjugate Targeting Tissue Factor Demonstrates Superior Preclinical Efficacy and Tolerability}},
author = {Thomas T. Poulsen and Olga Ilina and Jonathan H. Wardman and Anne Bie and Jette Bornholdt and Mette Gillberg and Daniela Pontieri and Pernille Barkholt and Christophe Côme and Yue Zhang and Jianjian Zhang and Yixuan Wang and Huiyan Shi and Shu-Hui Liu and Xun Meng and Dominik Mumberg},
journal = {Molecular Cancer Therapeutics},
year = {2026},
month = may,
doi = {10.1158/1535-7163.mct-26-0045},
url = {https://doi.org/10.1158/1535-7163.mct-26-0045},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - ADCE-T02: A Next-generation Antibody–Drug Conjugate Targeting Tissue Factor Demonstrates Superior Preclinical Efficacy and Tolerability
AU - Thomas T. Poulsen
AU - Olga Ilina
AU - Jonathan H. Wardman
AU - Anne Bie
AU - Jette Bornholdt
AU - Mette Gillberg
AU - Daniela Pontieri
AU - Pernille Barkholt
AU - Christophe Côme
AU - Yue Zhang
AU - Jianjian Zhang
AU - Yixuan Wang
AU - Huiyan Shi
AU - Shu-Hui Liu
AU - Xun Meng
AU - Dominik Mumberg
PY - 2026
DA - 2026/05/25
JO - Molecular Cancer Therapeutics
DO - 10.1158/1535-7163.mct-26-0045
UR - https://doi.org/10.1158/1535-7163.mct-26-0045
AB - Tissue factor (TF) protein is involved in activating the extrinsic blood coagulation cascade. TF expression is normally anatomically limited to the perivascular space, but TF is overexpressed in many malignancies, including pancreatic, cervical, prostate, and head and neck cancers, which makes TF an ideal antibody–drug conjugate (ADC) target. The TF-ADC tisotumab vedotin is approved for cervical cancer treatment but induces substantial side effects including ocular toxicities, peripheral neuropathy, and bleeding, limiting its further clinical development and warranting optimized ADC design to improve the therapeutic window. ADCE-T02 is a novel TF-ADC comprising the monoclonal antibody Ab-T02 conjugated via a self-immolative linker to the topoisomerase 1 inhibitor exatecan at an average drug-to-antibody ratio of 4.5. In contrast to tisotumab, Ab-T02 does not inhibit coagulation factor X activation. ADCE-T02 binds TF with high affinity inducing ADC internalization, exatecan release, cancer cell death, and bystander cytotoxicity in vitro. In vivo, ADCE-T02 is highly efficacious across a range of cell line–derived and patient-derived xenograft models including hard-to-treat models with large tumors, resistance to standard of care, low and/or heterogeneous expression of TF, and multidrug resistance. Importantly, ADCE-T02 demonstrates favorable pharmacokinetic properties and is well tolerated in nonhuman primates and in contrast to tisotumab vedotin and other auristatin-based ADCs shows no evidence of ocular, skin, and lung toxicities; peripheral nerve damage; or bleeding. In summary, ADCE-T02 constitutes a novel TF-ADC with a much improved preclinical therapeutic window. Phase I clinical development of ADCE-T02 in patients with advanced solid tumors is ongoing (ClinicalTrials ID: NCT06597721).
SN - 1535-7163
SN - 1538-8514
ER -