RT Journal Article
T1 Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR
A1 Compte, Marta
A1 Harwood, Seandean L.
A1 Martínez-Torrecuadrada, Jorge
A1 Pérez-Chacón, Gema
A1 González-García, Patricia
A1 Tapia-Galisteo, Antonio
A1 Bergen en Henegouwen, Paul M. P. Van
A1 Sánchez Muñoz, Aranzazu
A1 Fabregat, Isabel
A1 Sanz, Laura
A1 Zapata, Juan M.
A1 Álvarez-Vallina, Luis
A2 Palazon, Asis
AB Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BBagonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcgR interactions in the  major offtumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemiccancer immunotherapy protocols.
SN 1664-3224
YR 2021
FD 2021-01-07
LK https://hdl.handle.net/20.500.14352/107126
UL https://hdl.handle.net/20.500.14352/107126
LA eng
NO Compte, Marta, et al. «Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR». Frontiers in Immunology, vol. 11, enero de 2021, p. 614363. DOI.org (Crossref), https://doi.org/10.3389/fimmu.2020.614363.
NO Ministerio de Ciencia e Innovación
NO Ministerio de Economía y Competitividad
NO Instituto de Salud Carlos III
NO FEDER
NO Asociación Española contra el Cáncer
DS Docta Complutense
RD 29 may 2025