Secretory production of biologically active rat interleukin-2 by Clostridium acetobutylicum DSM792 as a tool for anti-tumor treatment.
The search for effective means of selectively delivering high therapeutic doses of anti-cancer agents to tumors has explored a variety of systems in the last decade. The ability of intravenously injected clostridial spores to infiltrate and thence selectively germinate in the hypoxic regions of solid tumors is exquisitely specific, making this system an interesting addition to the anti-cancer therapy arsenal. To increase the number of therapeutic proteins potentially useful for cancer treatment we have tested the possibility of Clostridium acetobutylicum to secrete rat interleukin-2 (rIL2). Therefore, rIL2 cDNA was placed under the control of the endo-beta-1,4-glucanase promoter and signal sequence of C. saccharobutylicum. Recombinant C. acetobutylicum containing the relevant construct secreted up to 800 microgl(-1) biologically active rIL2. The obtained yield should be sufficient to provoke in vivo effects.
Barbé
Sofie
S
Laboratory of Bacteriology, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Van Mellaert
Lieve
L
Theys
Jan
J
Geukens
Nick
N
Lammertyn
Elke
E
Lambin
Philippe
P
Anné
Jozef
J
D000818:Animals; D019677:Artificial Gene Fusion; D002480:Cellulase / Q000235:genetics; D046969:Clostridium acetobutylicum / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic; D021382:Protein Sorting Signals; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D018076:DNA, Complementary; D007376:Interleukin-2; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D002480:Cellulase