Nejvíce citovaný článek - PubMed ID 15274294
The application of the phagocytic receptor agonists in cancer immunotherapy was studied. Agonists (laminarin, molecules with terminal mannose, N-Formyl-methioninyl-leucyl-phenylalanine) were firmly anchored to the tumor cell surface. When particular agonists of phagocytic receptors were used together with LPS (Toll-like receptor agonist), high synergy causing tumour shrinkage and a temporary or permanent disappearance was observed. Methods of anchoring phagocytic receptor agonists (charge interactions, anchoring based on hydrophobic chains, covalent bonds) and various regimes of phagocytic agonist/LPS mixture applications were tested to achieve maximum therapeutic effect. Combinations of mannan/LPS and f-MLF/LPS (hydrophobic anchors) in appropriate (pulse) regimes resulted in an 80% and 60% recovery for mice, respectively. We propose that substantial synergy between agonists of phagocytic and Toll-like receptors (TLR) is based on two events. The TLR ligand induces early and massive inflammatory infiltration of tumors. The effect of this cell infiltrate is directed towards tumor cells, bearing agonists of phagocytic receptors on their surface. The result of these processes was effective killing of tumor cells. This novel approach represents exploitation of innate immunity mechanisms for treating cancer.
- MeSH
- aktivace makrofágů účinky léků MeSH
- analýza přežití MeSH
- cytokiny metabolismus MeSH
- glukany MeSH
- imunoterapie * MeSH
- ligandy MeSH
- lipopolysacharidy farmakologie MeSH
- mannosa chemie MeSH
- melanom experimentální farmakoterapie imunologie patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- polysacharidy farmakologie terapeutické užití MeSH
- proliferace buněk účinky léků MeSH
- průtoková cytometrie MeSH
- receptory imunologické agonisté metabolismus MeSH
- signální transdukce účinky léků MeSH
- toll-like receptory metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- glukany MeSH
- laminaran MeSH Prohlížeč
- ligandy MeSH
- lipopolysacharidy MeSH
- mannosa MeSH
- phagocytosis receptor MeSH Prohlížeč
- polysacharidy MeSH
- receptory imunologické MeSH
- toll-like receptory MeSH