title: Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2.
abstract: ScFv(FRP5)-ETA is a recombinant single-chain antibody-toxin with binding specificity for ErbB2/HER2. Previously potent antitumoral activity of the molecule against ErbB2 overexpressing tumor cells was demonstrated in vitro and in animal models. Here we report on the first application of scFv(FRP5)-ETA in human cancer patients summarizing case reports collected in four different clinical centers. Eleven patients suffering from metastatic breast and colorectal cancers and from malignant melanoma were treated on a compassionate-use basis by intratumoral injection of scFv(FRP5)-ETA into cutaneous lesions once daily for 7-10 days. Total daily doses ranged from 60 to 900 microg, and total doses per treatment cycle ranged from 0.6 to 6.0 mg. Treatment caused injected tumors to shrink in six of the 10 cases evaluated (60%). Complete regression of injected tumor nodules was accomplished in four patients (40%) and partial reduction in tumor size in another two patients (20%). Adverse reactions were restricted to local symptoms such as pain and inflammation at injection sites which were fully reversible. Only in one patient treated at the highest daily doses systemic liver toxicity of grade 2 was observed and treatment was discontinued on day 7. No hematologic, renal, and/or cardiovascular toxicities were noted. Our results demonstrate that local therapy with scFv(FRP5)-ETA can be effective against ErbB2 expressing tumors justifying further clinical development of this reagent.
authors.affiliation: Tumor Biology Center, Freiburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Azemar
authors.forename: Sirus
authors.initials: S
authors.lastname: Djahansouzi
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Maurer
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Clemens
authors.initials: C
authors.lastname: Unger
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Peter
authors.initials: P
authors.lastname: Dall
authors.forename: Bernd
authors.initials: B
authors.lastname: Groner
authors.forename: Winfried S
authors.initials: WS
authors.lastname: Wels
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008297:Male; D008545:Melanoma / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins