[Proapoptotic antibodies as new therapeutic agents for tumor treatment].
To convert the concept already successful in mice into clinical practice and commercialize it, a human anti-CD95-antibody must be produced. In a second step experiments must be performed on various normal healthy cells and tissues to determine whether these human anti-CD95-antibodies administered in very low doses have any effect on human cells (particularly hepatocytes) or at least cause only minimal side effects. If these studies yield positive results, then clinical trials can be conducted in which increasing doses are given to exclude an acute hepatotoxic effect and then the effect exerted by the antibody in combination with irradiation on tumor growth can be investigated.The advantage of this concept lies in the fact that systemic stimulus (low doses of anti-CD95-antibodies) is highly intensified by local radiotherapy and only then initiates cell death. Since the anti-CD95-antibodies trigger apoptosis primarily in tumor endothelia, this approach could be employed not only for prostate cancer and melanomas, which have already been tested, but also for many other tumors.
Schenck
M
M
Molekularbiologische und urologische Forschergruppe, Urologische Universitätsklinik, Hufelandstrasse 55, 45122 Essen. marcus.schenck@uni-due.de
Börgermann
C
C
vom Dorp
F
F
Groneberg
M
M
Busch
Y
Y
Carpinteiro
A
A
Wilker
B
B
Keitsch
S
S
Moyrer
S
S
Schmid
K W
KW
Stuschke
M
M
Rübben
H
H
Gulbins
E
E
D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D011471:Prostatic Neoplasms / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects*; D019014:fas Receptor / Q000276:immunology*
D000906:Antibodies; D002518:Ceramides; D019014:fas Receptor; D013108:Sphingomyelin Phosphodiesterase