Article ; Online: Accum™ Technology: A Novel Conjugable Primer for Onco-Immunotherapy.
Molecules (Basel, Switzerland)
2022 Volume 27, Issue 12
Abstract: Compromised activity is a common impediment for biologics requiring endosome trafficking into target cells. In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or subsequently pumped extracellularly, leading to a reduction in ... ...
| Abstract | Compromised activity is a common impediment for biologics requiring endosome trafficking into target cells. In cancer cells, antibody-drug conjugates (ADCs) are trapped in endosomes or subsequently pumped extracellularly, leading to a reduction in intracellular accumulation. In subsets of dendritic cells (DCs), endosome-engulfed antigens face non-specific proteolysis and collateral damage to epitope immunogenicity before proteasomal processing and subsequent surface presentation. To bypass these shortcomings, we devised Accum™, a conjugable biotechnology harboring cholic acid (ChAc) and a nuclear localization signal (NLS) sequence for endosome escape and prompt nuclear targeting. Combined, these mechanisms culminate in enhanced intracellular accumulation and functionalization of coupled biologics. As proof-of-principle, we have biochemically characterized Accum, demonstrating its adaptability to ADCs or antigens in different cancer settings. Additionally, we have validated that endosome escape and nuclear routing are indispensable for effective intracellular accumulation and guaranteed target cell selectivity. Importantly, we have demonstrated that the unique mechanism of action of Accum translates into enhanced tumor cytotoxicity when coupled to ADCs, and durable therapeutic and prophylactic anti-cancer immunogenicity when coupled to tumor antigens. As more pre-clinical evidence accumulates, the adaptability, unique mechanism of action, and high therapeutic potency of Accum signal a promising transition into clinical investigations in the context of onco-immunotherapy. |
|---|---|
| MeSH term(s) | Antigens, Neoplasm ; Biological Products/pharmacology ; Endosomes ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Immunotherapy ; Nuclear Localization Signals/chemistry |
| Chemical Substances | Antigens, Neoplasm ; Biological Products ; Immunoconjugates ; Nuclear Localization Signals |
| Language | English |
| Publishing date | 2022-06-13 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Review |
| ZDB-ID | 1413402-0 |
| ISSN | 1420-3049 ; 1431-5165 ; 1420-3049 |
| ISSN (online) | 1420-3049 |
| ISSN | 1431-5165 ; 1420-3049 |
| DOI | 10.3390/molecules27123807 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.MO 81: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.