| Autor: |
Vigo M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Biomedicine Doctorate Program, University of Barcelona, Barcelona, Spain., Placci M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Biotechnology Doctorate Program, University of Barcelona, Barcelona, Spain., Muro S; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain.; Institution of Catalonia for Research and Advanced Studies (ICREA), Barcelona, Spain. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of drug targeting [J Drug Target] 2024 Dec 17, pp. 1-13. Date of Electronic Publication: 2024 Dec 17. |
| DOI: |
10.1080/1061186X.2024.2438884 |
| Abstrakt: |
Drug targeting can be achieved by coupling drugs or their carriers to affinity molecules, mostly antibodies (Abs), which recognise specific protein targets. However, most proteins are not expressed in an exclusive configuration but as various isoforms. Hence, selected targeting molecules may fail to target with enough efficiency in clinical trials, which is overlooked. We illustrate this by targeting intercellular adhesion molecule 1 (ICAM-1), a cell-surface protein overexpressed in many pathologies. Most ICAM-1 targeting studies used Ab R6.5, which binds ICAM-1 domain 2 (D2). Yet, literature and our data show that D2 is frequently absent among ICAM-1 isoforms. We thus produced a battery of five new Abs (B4, B6, B11, C12 and G2) and tested their ability to recognise both full-length and -D2 ICAM-1. In solution, all Abs recognised both ICAM-1 forms (from 5.3 × 10 11 to 4.2 × 10 12 sum intensity/well). Coating them on nanocarriers (NCs) rendered G2 specific against -D2 ICAM-1 (4.2 × 10 6 NCs/well) while other Abs kept their dual recognition (from 6.4 × 10 6 to 2.2 × 10 7 NCs/well). All Abs induced NC intracellular uptake in respective cells (from 42% to 85%) and displayed good cross-species reactivity (from 4.4 × 10 11 to 2.6 × 10 12 sum intensity/well). These Abs represent valuable tools to target ICAM-1 and illustrate a new targeting paradigm that may improve classical strategies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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