6533b85ffe1ef96bd12c11cc

RESEARCH PRODUCT

Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.

Alexandra S RothKatalin KarikóÖZlem TüreciBernhard HebichRené P RothUgur SahinLeyla CelikChristiane StadlerHayat Bähr-mahmud

subject

0301 basic medicineMaleBispecific antibodyT-LymphocytesImmunoblottingEndogenyEnzyme-Linked Immunosorbent AssayIn Vitro TechniquesGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesMiceMice Inbred NODCell Line TumorNeoplasmsAntibodies BispecificMedicineAnimalsHumansRNA MessengerMessenger RNAMice Inbred BALB Cbiologybusiness.industryRNAGeneral MedicineMolecular biologyImmunohistochemistryXenograft Model Antitumor AssaysTumor Burden030104 developmental biologyCell cultureDrug deliveryLuminescent Measurementsbiology.proteinImmunohistochemistryCytokinesFemaleAntibodybusiness

description

The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.

10.1038/nm.4356https://pubmed.ncbi.nlm.nih.gov/28985209