TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging

  • Authors:
    • Elisa Tremante
    • Leonardo Sibilio
    • Fabio Centola
    • Nadine Knutti
    • Gerd Holzapfel
    • Isabella Manni
    • Matteo Allegretti
    • Paolo Lombardi
    • Loredana Cecchetelli
    • Karlheinz Friedrich
    • Joachim Bertram
    • Patrizio Giacomini
  • View Affiliations

  • Published online on: March 26, 2021     https://doi.org/10.3892/or.2021.8028
  • Article Number: 77
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Herein, we describe TOOLBOX, a 3‑step modular nano‑assembly targeting system that permits the combinatorial exchange of antibody specificities and toxic payloads, introducing modularity in antibody‑drug conjugate (ADC) manufacturing. TOOLBOX integrates 3 building blocks: i) a recombinant antibody fragment (that in the selected setting targets the proto‑oncogene ERBB2) genetically fused to an 8 amino acid Strep‑Tag®; ii) a multivalent protein adapter, called Strep‑Tactin®; iii) two anticancer agents, e.g. DNA nanobinders and the maytansinoid DM1, both carrying a chemically attached Strep‑Tag that reversibly turns them into inactive prodrugs. Stoichiometrically optimized complexes of Strep‑Tagged antibody fragments and drugs, bridged by Strep‑Tactin, were specifically uptaken by breast cancer cells expressing ERBB2, and this unexpectedly resulted in conditional prodrug reactivation. A promoter‑reporter system showed that TOOLBOX inhibited downstream ERBB2 signaling not only in ERBB2‑overexpressing/‑amplified SK‑BR‑3 cells grown in vitro, but also in ERBB2‑low/non‑amplified BRC230 triple‑negative breast carcinoma cells xenotransplanted in nude mice. Thus, TOOLBOX is a modular ADC‑like nano‑assembly platform for precision oncology.
View Figures
View References

Related Articles

Journal Cover

May-2021
Volume 45 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Tremante E, Sibilio L, Centola F, Knutti N, Holzapfel G, Manni I, Allegretti M, Lombardi P, Cecchetelli L, Friedrich K, Friedrich K, et al: TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging. Oncol Rep 45: 77, 2021
APA
Tremante, E., Sibilio, L., Centola, F., Knutti, N., Holzapfel, G., Manni, I. ... Giacomini, P. (2021). TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging. Oncology Reports, 45, 77. https://doi.org/10.3892/or.2021.8028
MLA
Tremante, E., Sibilio, L., Centola, F., Knutti, N., Holzapfel, G., Manni, I., Allegretti, M., Lombardi, P., Cecchetelli, L., Friedrich, K., Bertram, J., Giacomini, P."TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging". Oncology Reports 45.5 (2021): 77.
Chicago
Tremante, E., Sibilio, L., Centola, F., Knutti, N., Holzapfel, G., Manni, I., Allegretti, M., Lombardi, P., Cecchetelli, L., Friedrich, K., Bertram, J., Giacomini, P."TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging". Oncology Reports 45, no. 5 (2021): 77. https://doi.org/10.3892/or.2021.8028