RT Journal Article
T1 Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer
A1 Tapia Galisteo, Antonio
A1 Aguilar Sopeña, Óscar
A1 Narbona Corral, Javier
A1 Lacadena García-Gallo, Francisco Javier
A1 Roda Navarro, Pedro
A1 Sanz, Laura
AB 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.
PB Taylor and Francis
SN 2162-402X
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/120124
UL https://hdl.handle.net/20.500.14352/120124
LA eng
NO 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
NO Fondos FEDER
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Comunidad Autónoma de Madrid
NO Instituto de Salud Carlos III (España)
NO Asociación Española Contra el Cáncer
DS Docta Complutense
RD 17 may 2025