2026-06-07T23:47:44Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1201242025-11-12T09:35:12Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Tapia Galisteo, Antonio author Aguilar Sopeña, Óscar author Narbona Corral, Javier author Lacadena García-Gallo, Francisco Javier author Roda Navarro, Pedro author Sanz, Laura author 2022 Retargeting of T lymphocytes toward cancer cells by bispecific antibodies has demonstrated its therapeutic potential, with one such antibody approved for the treatment of acute lymphoblastic leukemia (blinatumomab) and several other in clinical trials. However, improvement of their efficacy and selectivity for solid tumors is still required. Here, we describe a novel tandem T-cell recruiting trispecific antibody for the treatment of colorectal cancer (CRC). This construct, termed trispecific T-cell engager (TriTE), consists of a CD3-specific single-chain Fv (scFv) flanked by anti-epidermal growth factor receptor (EGFR) and anti-epithelial cell adhesion molecule (EpCAM) single-domain V antibodies. The TriTE was well expressed in mammalian and yeast cells, bound the cognate antigens of the three parental antibodies, and enabled the specific cytolysis of EGFR- and/or EpCAM-expressing cancer cells, without inducing T cell activation and cytoxicity against double-negative (EGFREpCAM) cancer cells. Bivalent bispecific targeting of double-positive HCT116 cells by TriTE improved potency up to 100-fold compared to single-positive cells and significantly prolonged survival . In addition, it was less efficient at killing single-positive target cells than the corresponding bispecific controls, leading to potentially enhanced tumor specificity. Moreover, dual targeting of two tumor-associated antigens may contribute toward preventing the tumor escape by antigen loss caused by selective pressures from conventional single-targeting T-cell engagers, and may help to overcome antigenic heterogeneity. Tapia-Galisteo, A., Sánchez Rodríguez, Í., Aguilar-Sopeña, O., Harwood, S. L., Narbona, J., Ferreras Gutierrez, M., … Sanz, L. (2022). Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer. OncoImmunology, 11(1). https://doi.org/10.1080/2162402X.2022.2034355 2162-402X 10.1080/2162402X.2022.2034355 https://hdl.handle.net/20.500.14352/120124 https://doi.org/10.1080/2162402X.2022.2034355 35154908 https://www.tandfonline.com/doi/full/10.1080/2162402X.2022.2034355 https://pubmed.ncbi.nlm.nih.gov/35154908/ Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer