Targeting her-2/neu with antirat Neu virosomes for cancer therapy.
HER-2/neu (p185(HER2)) oncogene represents an attractive target for antibody-mediated immunotherapy. The major problem of combining chemotherapy and immunotherapy is the severe side effects that limit the use of doxorubicin (Doxo) as a cytotoxic drug. We have used virosomes (Vir; reconstituted fusion-active viral envelopes) as a new drug delivery system and have shown that Vir are capable of binding and penetrating into tumor cells, delivering cytotoxic drugs. We have additionally demonstrated that conjugating Fab' fragments of an antirat Neu (anti-rNeu) monoclonal antibody to Vir selectively and efficiently inhibits tumor progression of established rNeu-overexpressing breast tumors. Fab'-Doxo-Vir combine the antiproliferative properties of the monoclonal antibody and the cytotoxic effect of Doxo in vivo. Furthermore, Fab'-Doxo-Vir significantly inhibit tumor formation at a tumor load representing metastatic spread. These results indicate that Vir conjugated with an antibody against a tumor antigen are a promising new selective drug delivery system for the treatment of tumors expressing a specific tumor antigen.
Waelti
Ernst
E
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Wegmann
Nina
N
Schwaninger
Ruth
R
Wetterwald
Antionette
A
Wingenfeld
Carsten
C
Rothen-Rutishauser
Barbara
B
Gimmi
Claude D
CD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D000922:Immunotoxins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D022701:Virosomes
D000911:Antibodies, Monoclonal; D004317:Doxorubicin; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D022701:Virosomes