RT Journal Article
T1 A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows signifcantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts
A1 Lázaro Gorines, R.
A1 Ruiz de la Herrán, J.
A1 Navarro, R.
A1 Sanz, L.
A1 Alvarez Vallina, L.
A1 Martínez Del Pozo, Álvaro
A1 Gavilanes, José G.
A1 Lacadena García-Gallo, Francisco Javier
AB Immunotoxins are chimeric molecules, which combine antibody specifcity to recognize and bind with high-afnity tumor-associated antigens (TAA) with the potency of the enzymatic activity of a toxin, in order to induce the death of target cells. Current immunotoxins present some limitations for cancer therapy, driving the need to develop new prototypes with optimized properties. Herein we describe the production, purifcation and characterization of two new immunotoxins based on the gene fusion of the anti-carcinoembryonic antigen (CEA) single-chain variable fragment (scFv) antibody MFE23 to α-sarcin, a potent fungal ribotoxin. One construct corresponds to a conventional monomeric single-chain immunotoxin design (IMTXCEAαS), while the other one takes advantage of the trimerbody technology and exhibits a novel trimeric format (IMTXTRICEAαS) with enhanced properties compared with their monomeric counterparts, including size, functional afnity and biodistribution, which endow them with an improved tumor targeting capacity. Our results show the highly specifc cytotoxic activity of both immunotoxins in vitro, which was enhanced in the trimeric format compared to the monomeric version. Moreover, the trimeric immunotoxin also exhibited superior antitumor activity in vivo in mice bearing human colorectal cancer xenografts. Therefore, trimeric immunotoxins represent a further step in the development of next-generation therapeutic immunotoxins.
PB Nature Research
SN 2045-2322 (online)
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/13550
UL https://hdl.handle.net/20.500.14352/13550
LA eng
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 4 abr 2025