Localization and therapy of human cervical tumor xenografts with radiolabeled monoclonal antibody 1H10.
Murine IgG3 monoclonal antibody (Mab) 1H10, which recognizes a tumor-associated antigen expressed on the surface of more than 40% of human cervical carcinoma tissues, was used for in vivo localization and therapy of cervical tumor xenografts. A human cervical carcinoma cell line, CaSki, was used as our experimental tumor system. Mab 1H10 antigen expression on the surface of CaSki cells was found to be cell-cycle independent. The ability of Mab 1H10 F(ab')2 to bind to CaSki tumor xenografts was verified by direct immunohistochemical staining of thin tumor sections with a Mab 1H10-peroxidase conjugate. Radioimmunoscintigraphy of nude mice bearing CaSki tumors after iv administration of [131I]1H10 F(ab')2 showed clear tumor images 48 hr after Mab injection. Radiolabeled Mab 1H10 F(ab')2 was found to specifically localize in solid CaSki tumors 96 hr after antibody injection. Radioactivity in tumor tissue was 4 times higher than that in kidney tissue and over 6 times higher than that in liver tissue. Mab 1H10 F(ab')2 binding to xenografted CaSki tumors was 17 times greater than a control IgG3 F(ab')2 after 96 hr. Therapy of athymic mice bearing established CaSki tumors with three iv injections of 100 microCi [131I]1H10 F(ab')2 resulted in extensive tumor necrosis and significant suppression (p < 0.05) of tumor growth compared to that in control mice. These results indicate that Mab 1H10 F(ab')2 may be clinically useful for detection or treatment of cervical cancer.
Yu
M H
MH
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Roffler
S R
SR
Hwang
W S
WS
Tung
E
E
Chen
W L
WL
Yeh
M Y
MY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002453:Cell Cycle; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011863:Radioimmunoassay; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes