Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/32986
Title: Balanced secretion of anti-CEA × anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity.
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Issue Date: 2017
Citation: Gene Ther..2017 04;(24)4:208-214
Abstract: Adoptive transfer of genetically engineered human cells secreting bispecific T-cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs (single-chain variable fragments), because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T-cell activation. Here, we demonstrate that the incorporation of a 2A self-processing peptide derived from foot-and-mouth disease virus conveying co-translational cleavage into a two-chain anti-CD3 × anti-CEA diabody gene enables near-equimolar expression of diabody chains 1 and 2, and thus increases the final amount of assembled diabody. This was found to maximize diabody-mediated T-cell activation and cytotoxicity against carcinoembryonic antigen-positive tumor cells.
PMID: 28075428
URI: https://hdl.handle.net/20.500.12530/32986
Rights: openAccess
Appears in Collections:Hospitales > H. U. Puerta de Hierro Majadahonda > Artículos
Fundaciones e Institutos de Investigación > IIS H. U. Puerta de Hierro-Segovia de Arana > Artículos

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