Premium
Intra‐tumoral application of a heregulin‐exotoxin‐A fusion protein causes rapid tumor regression without adverse systemic or local effects
Author(s) -
Groner Bernd,
Wick Bettina,
Jeschke Margit,
Fiebig HeinzHerbert,
Dengler Wolfgang,
Runau Tatiana,
Mihatsch Michael,
Kahl Ralf,
Schmidt Mathias,
Wels Winfried,
Stöcklin Elisabeth
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970317)70:6<682::aid-ijc10>3.0.co;2-c
Subject(s) - adverse effect , pseudomonas exotoxin , medicine , regression , fusion protein , exotoxin , neuregulin , oncology , biology , toxin , psychology , microbiology and biotechnology , receptor , biochemistry , bacteria , gene , psychoanalysis , pseudomonas aeruginosa , genetics , recombinant dna
Tumor toxins are recombinant, bifunctional proteins which comprise a tumor‐cell‐specific recognition domain and an enzymatic toxin domain. We have evaluated the in vivo effects of a tumor toxin that specifically recognizes the erbB‐3 and erbB‐4 receptors (HRGβI‐ETA). High doses of HRGβI‐ETA administered systemically (intracardially or intraperitoneally) caused acute liver necrosis and were lethal. The same dose of tumor toxins applied subcutaneously had no detectable histopathological effects. The anti‐tumor activity of HRGβI‐ETA was tested in nude mice with xenografts of a human breast tumor, MAXFII62. The MAXFII62 tumor grew rapidly upon s.c. implantation. Intra‐tumoral application of HRGβI‐ETA (7 times 5 μg over a period of 21 days) induced complete regression of tumors. At the time the treatment was terminated, no tumor cells were detectable microscopically. Evaluation of the liver of treated animals revealed no significant toxicity in the effective dose range. These experiments indicate that tumor toxins can become valuable for local tumor treatment and for reduction of tumor burden. Int. J. Cancer 70:682–687, 1997. © 1997 Wiley‐Liss, Inc.