Novel Human Bispecific Aptamer-Antibody Conjugates for Efficient Cancer Cell Killing.

ABSTRACT: Monoclonal antibodies have been approved by the Food and Drug Administration for the treatment of various human cancers. More recently, oligonucleotide aptamers have risen increasing attention for cancer therapy thanks to their low size (efficient tumor penetration) and lack of immunogenicity, even though the short half-life and lack of effector functions still hinder their clinical applications. Here, we demonstrate, for the first time, that two novel bispecific conjugates, consisting of an anti-epidermal growth factor receptor (EGFR) aptamer linked either with an anti-epidermal growth factor receptor 2 (ErbB2) compact antibody or with an immunomodulatory (anti-PD-L1) antibody, were easily and rapidly obtained. These novel aptamer-antibody conjugates retain the targeting ability of both the parental moieties and acquire a more potent cancer cell killing activity by combining their inhibitory properties. Furthermore, the conjugation of the anti-EGFR aptamer with the immunomodulatory antibody allowed for the efficient redirection and activation of T cells against cancer cells, thus dramatically enhancing the cytotoxicity of the two conjugated partners. We think that these bispecific antibody-aptamer conjugates could have optimal biological features for therapeutic applications, such as increased specificity for tumor cells expressing both targets and improved pharmacokinetic and pharmacodynamic properties due to the combined advantages of the aptamer and antibody.

SUBMITTER: Passariello M 

PROVIDER: S-EPMC6770524 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature