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Optimization of cell-wall skeleton derived from Mycobacterium bovis BCG Tokyo 172 (SMP-105) emulsion in delayed-type hypersensitivity and antitumor models.
- Source :
-
Drug discoveries & therapeutics [Drug Discov Ther] 2012 Aug; Vol. 6 (4), pp. 218-25. - Publication Year :
- 2012
-
Abstract
- Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a potent adjuvant and has been shown to possess antitumor activity in many non-clinical and clinical studies. As there are no approved BCG-CWS formulations for cancer therapy, we investigated the potential for cancer immunotherapy of SMP-105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we compared the effects of drakeoland squalane-based SMP-105 emulsions on IFN-γ production in rats and evaluated their ability to induce skin reaction in guinea pigs. Both emulsions had the same activity in both experiments. We selected squalane as base material and produced two types of squalane-based formulations (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water emulsions. Although the vialed emulsion showed the same pattern of distribution as a usual homogenized emulsion, the pumped emulsion showed more uniform distribution than the other two emulsions. Whereas both emulsions enhanced strong delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped emulsion induced slightly smaller edema. Data on oil droplet size distribution suggest that few micrometer oil droplet size might be appropriate for oil-in-water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was stronger than that of some of the launched toll-like receptor (TLR) agonists (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited antitumor effectiveness, while Immunobladder had almost the same effect as SMP-105 at the highest dose, but needed about 10 times the amount of SMP-105. These findings first indicate that SMP-105 has great potential in cancer immunotherapy.
- Subjects :
- Adjuvants, Immunologic adverse effects
Adjuvants, Immunologic isolation & purification
Animals
Antineoplastic Agents adverse effects
Antineoplastic Agents isolation & purification
Cell Line, Tumor
Cell Wall Skeleton adverse effects
Cell Wall Skeleton isolation & purification
Emulsions
Female
Guinea Pigs
Hypersensitivity, Delayed immunology
Immunotherapy
Interferon-gamma biosynthesis
Interferon-gamma immunology
Liver Neoplasms, Experimental drug therapy
Liver Neoplasms, Experimental immunology
Male
Mice
Mice, Inbred C57BL
Rats
Rats, Inbred Lew
Xenograft Model Antitumor Assays
Adjuvants, Immunologic pharmacology
Antineoplastic Agents pharmacology
Cell Wall Skeleton pharmacology
Mycobacterium bovis chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1881-7831
- Volume :
- 6
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Drug discoveries & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 23006993