title: CD28 aptamers as powerful immune response modulators.
abstract: CD28 is one of the main costimulatory receptors responsible for the proper activation of T lymphocytes. We have isolated two aptamers that bind to the CD28 receptor. As a monomer, one of them interfered with the binding of CD28 to its ligand (B7), precluding the costimulatory signal, whereas the other one was inactive. However, dimerization of any of the anti-CD28 aptamers was sufficient to provide an artificial costimulatory signal. No antibody has featured a dual function (i.e., the ability to work as agonist and antagonist) to date. Two different agonistic structures were engineered for each anti-CD28 aptamer. One showed remarkably improved costimulatory properties, surpassing the agonistic effect of an anti-CD28 antibody. Moreover, we showed in vivo that the CD28 agonistic aptamer is capable of enhancing the cellular immune response against a lymphoma idiotype and of prolonging survival of mice which receive the aptamer together with an idiotype vaccine. The CD28 aptamers described in this work could be used to modulate the immune response either blocking the interaction with B7 or enhancing vaccine-induced immune responses in cancer immunotherapy.Molecular Therapy - Nucleic Acids (2013) 2, e98; doi:10.1038/mtna.2013.26; published online 11 June 2013.
authors.affiliation: Laboratory of Immunotherapy, Oncology Division, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pastor
authors.forename: Mario M
authors.initials: MM
authors.lastname: Soldevilla
authors.forename: Helena
authors.initials: H
authors.lastname: Villanueva
authors.forename: Despina
authors.initials: D
authors.lastname: Kolonias
authors.forename: Susana
authors.initials: S
authors.lastname: Inoges
authors.forename: Ascensión L
authors.initials: AL
authors.lastname: de Cerio
authors.forename: Romy
authors.initials: R
authors.lastname: Kandzia
authors.forename: Victor
authors.initials: V
authors.lastname: Klimyuk
authors.forename: Yuri
authors.initials: Y
authors.lastname: Gleba
authors.forename: Eli
authors.initials: E
authors.lastname: Gilboa
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bendandi