BibTex format

author = {Compte, M and Lykke, Harwood S and Munoz, IG and Navarro, R and Zonca, M and Perez-Chacon, G and Erce-Llamazares, A and Merino, N and Tapia-Galisteo, A and Cuesta, AM and Mikkelsen, K and Caleiras, E and Nunez-Prado, N and Aznar, MA and Lykkemark, S and Martinez-Torrecuadrada, J and Melero, I and Blanco, FJ and Bernardino, de la Serna J and Zapata, JM and Sanz, L and Alvarez-Vallina, L},
doi = {10.1038/s41467-018-07195-w},
journal = {Nature Communications},
title = {A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity},
url = {},
volume = {9},
year = {2018}

RIS format (EndNote, RefMan)

AB - The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcγR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8N/CEGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8N/CEGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8N/CEGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate FcγR interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy.
AU - Compte,M
AU - Lykke,Harwood S
AU - Munoz,IG
AU - Navarro,R
AU - Zonca,M
AU - Perez-Chacon,G
AU - Erce-Llamazares,A
AU - Merino,N
AU - Tapia-Galisteo,A
AU - Cuesta,AM
AU - Mikkelsen,K
AU - Caleiras,E
AU - Nunez-Prado,N
AU - Aznar,MA
AU - Lykkemark,S
AU - Martinez-Torrecuadrada,J
AU - Melero,I
AU - Blanco,FJ
AU - Bernardino,de la Serna J
AU - Zapata,JM
AU - Sanz,L
AU - Alvarez-Vallina,L
DO - 10.1038/s41467-018-07195-w
PY - 2018///
SN - 2041-1723
TI - A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity
T2 - Nature Communications
UR -
UR -
UR -
VL - 9
ER -