TOOLBOX: Strep­Tagged nano­assemblies of antibody­drug­conjugates (ADC) for modular and conditional cancer drugging

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.

[Corrigendum] TOOLBOX: Strep­Tagged nano­assemblies of antibody­drug­conjugates (ADC) for modular and conditional cancer drugging.

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].