Pretargeted radioimmunotherapy.
This brief review covers the concept of pretargeted radioimmunotherapy and summarize the results obtained in preclinical animal models and initial phase I clinical trials. Reagents studied have been a bifunctional antibody prepared by crosslinking Fab' fragments from two antibodies with different specificity, one binding the target antigen expressed on tumors and the other binding a radiolabeled peptide. The alternative system is a conjugate of streptavidin linked to the pretargeting agent and radiolabeled biotin. After reaching optimal tumor targeting of the pretargeting agent, a synthetic mono-biotin poly N-acetyl-galactosamine compound was used to clear unbound targeting agent from the circulation before the injection of radiolabeled biotin. Promising therapeutic responses were obtained in various tumor xenograft models in athymic nude mice. A phase I study of an anti-CD20/streptavidin pretargeting agent and 15 mCi/m(2)(90)Y-biotin produced objective responses with minimal toxicity among lymphoma patients, with an average tumor-to-whole-body radiation dose ratio of 49. Pretargeting radioimmunotherapy approaches have shown higher tumor-to-whole-body ratios than that usually obtained with one-step radioimmunotherapy.
Meredith
Ruby F
RF
Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Buchsbaum
Donald J
DJ
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001710:Biotin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D019809:Streptavidin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D015021:Yttrium Radioisotopes; D001710:Biotin; D019809:Streptavidin