- An Enzyme-Directed Imidazoquinoline for Cancer Immunotherapy
-
Herein we report the synthesis and activity of an enzyme-directed immunostimulant with immune cell activation mediated by β-galactosidase, either exogenously added, or on B16 melanoma cells. Covalent attachment of a β-galactopyranoside to an imidazoquinoline immunostimulant at a position critical for activity resulted in a pro-immunostimulant that could be selectively converted by β-galactosidase into an active immunostimulant. The pro-immunostimulant exhibited β-galactosidase-directed immune cell activation as measured by NF-κB transcription in RAW-Blue macrophages or cytokine production (TNF, IL-6, IL-12) in JAWSII monocytes. Conversion of the pro-immunostimulant into an active immunostimulant was also found to occur using β-galactosidase-enriched B16 melanoma cells. In co-culture experiments with either immune cell line, β-galactosidase-enriched B16 cells effected activation of bystander immune cells.
- Hantho, Joseph D.,Strayer, Timothy A.,Nielsen, Amy E.,Mancini, Rock J.
-
-
Read Online
- FLUOROGENIC GLYCOSIDASE SUBSTRATE AND ASSOCIATED DETECTION METHOD
-
The invention relates to novel glycosidase substrates of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R′9, V, X, Y and Z are as defined in claim 1, and a method for detecting the presence of a catalytically active glycosidase by means of one of said substrates.
- -
-
-
- ENZYME-DIRECTED IMMUNOSTIMULANT AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATION(S)
-
The disclosed invention relates to the novel composition of matter that allows for the controlled release of highly active compounds to be delivered to a desired site. This novel composition utilizes the immune system to allow for the controlled release of desired compounds. The present invention can utilize a plurality of highly active compounds, with one embodiment being the use of chemotherapeutics for the treatment of cancer.
- -
-
-
- Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity
-
The synthesis of the first spacer containing, duocarmycin analogue prodrug 11 was realised, its biological properties evaluated and compared to its counterpart prodrug 2 without a spacer unit. The synthesis comprises the manufacture of the new acetylated
- Schuster, Heiko J.,Krewer, Birgit,Von Hof, J. Marian,Schmuck, Kianga,Schuberth, Ingrid,Alves, Frauke,Tietze, Lutz F.
-
experimental part
p. 1833 - 1842
(2010/08/21)
-