Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy.
This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.
Goldenberg
David M
DM
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA. dmg.gscancer@att.net
Sharkey
Robert M
RM
Paganelli
Giovanni
G
Barbet
Jacques
J
Chatal
Jean-François
JF
D000912:Antibodies, Neoplasm / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000628:therapy; D002986:Clinical Trials as Topic; D005910:Glioma / Q000000981:diagnostic imaging / Q000628:therapy; D006241:Haptens; D006801:Humans; D007202:Indicators and Reagents; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy; D016719:Radioimmunodetection / Q000379:methods*; D016499:Radioimmunotherapy / Q000379:methods*; D019809:Streptavidin; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy
D000912:Antibodies, Neoplasm; D006241:Haptens; D007202:Indicators and Reagents; D019809:Streptavidin