RESUMEN
Herein, we describe TOOLBOX, a 3step modular nanoassembly targeting system that permits the combinatorial exchange of antibody specificities and toxic payloads, introducing modularity in antibodydrug conjugate (ADC) manufacturing. TOOLBOX integrates 3 building blocks: i) a recombinant antibody fragment (that in the selected setting targets the protooncogene ERBB2) genetically fused to an 8 amino acid StrepTag®; ii) a multivalent protein adapter, called StrepTactin®; iii) two anticancer agents, e.g. DNA nanobinders and the maytansinoid DM1, both carrying a chemically attached StrepTag that reversibly turns them into inactive prodrugs. Stoichiometrically optimized complexes of StrepTagged antibody fragments and drugs, bridged by StrepTactin, were specifically uptaken by breast cancer cells expressing ERBB2, and this unexpectedly resulted in conditional prodrug reactivation. A promoterreporter system showed that TOOLBOX inhibited downstream ERBB2 signaling not only in ERBB2overexpressing/amplified SKBR3 cells grown in vitro, but also in ERBB2low/nonamplified BRC230 triplenegative breast carcinoma cells xenotransplanted in nude mice. Thus, TOOLBOX is a modular ADClike nanoassembly platform for precision oncology.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Inmunoconjugados/administración & dosificación , Nanoestructuras/administración & dosificación , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Neoplasias de la Mama/inmunología , Línea Celular Tumoral , Humanos , Inmunoconjugados/química , Ratones , Ratones Desnudos , Nanoestructuras/química , Receptor ErbB-2/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Following the publication of the above article, the authors have requested a change in the authorship on the paper, and the revised list of authors is presented above; essentially, the ninth intended author, Giuseppe Salvo (G.S.), was inadverently omitted from the author list. G.S. contributed towards the T design and the preparation of the tagged ScFv. Therefore, the revised authors' names and affiliations, as they should have been presented in the original version of this paper, are as follows: Elisa Tremante1, Leonardo Sibilio2,7, Fabio Centola2,8, Nadine Knutti3,9, Gerd Holzapfel4, Isabella Manni5, Matteo Allegretti1, Paolo Lombardi6, Giuseppe Salvo2,10, Loredana Cecchetelli2, Karlheinz Friedrich3, Joachim BertraM4 and Patrizio Giacomini1. 1Oncogenomics and Epigenetics, IRCCS Regina Elena National Cancer Institute, Rome; 2Ibi Lorenzini, Aprilia, Italy; 3University Hospital Jena, Institute of Biochemistry II, Jena; 4IBA GmbH, Göttingen, Germany; 5SAFU, IRCCS Regina Elena National Cancer Institute, Rome; 6NaxosPharma, Novate Milanese, Milan, Italy. Correspondence to: Dr Patrizio Giacomini. Oncogenomics and Epigenetics, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. Email: patrizio.giacomini@ifo.gov.it. Present address: 7Menarini Biotech, Pomezia, Rome, Italy. Present address: 8Merck Serono Spa, Global Analytical Department, Guidonia Montecelio, Rome, Italy. Present address: 9University Hospital Jena Institute for Clinical Chemistry and Laboratory Diagnostics, Jena, Germany. Present address: 10External Quality Assurance (ExM), MSD Italia S.r.l., Via Vitorchiano 151, 00189 Rome.Italy. Furthermore, the Authors' contributions section should be amended to read as follows: Authors' contributions: ET and MA tested the TOOLBOX concept and performed the flow cytometry experiments. LS, FC, GS and LC designed and prepared the tagged ScFv. NK and KF designed and prepared the GFP promoterreporter construct. GH and JB designed and manufactured StrepTactins. ET and IM performed animal studies. PL designed and manufactured NAX and NAXT compounds. PG conceptualized TOOLBOX and wrote the manuscript with the contribution of all authors. All authors have approved the final version of the manuscript. All the authors agree with the inclusion of Giuseppe Salvo as an author on this paper, and are grateful to the Editor for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 45: 77, 2021; DOI: 10.3892/or.2021.8028].