Comparison of 131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts.
Three human ovarian cancer xenografts of different origin and grown s.c. in nude mice as well-established tumors were studied for their sensitivity to cisplatin (CDDP), cyclophosphamide (CTX), 131I-labelled anti-episialin monoclonal antibody (MAb) 139H2, or external-beam radiotherapy. The maximum tolerated dose of CDDP given weekly i.v. x 2 induced a tumor growth inhibition (GI) of 77.5% and 85.1% of the serous xenografts Ov.Ri(C) and OVCAR-3, respectively. The mucinous xenograft Ov.Pe was relatively resistant to CDDP. The maximum tolerated dose of CTX, given i.p. x 2 with a 2-week interval, induced a GI between 52.9% and 59.7% for each of the 3 xenografts. Radioimmunotherapy with 500-750 microCi 131I-specific MAb 139H2, administered i.v. x 2 with a 2-week interval, was more effective than CDDP or CTX. The 500 microCi 131I-MAb 139H2 schedule induced 100% GI in Ov.Ri(C) xenografts and all tumors were cured. The same schedule was slightly less effective in OVCAR-3 xenografts, but complete tumor regressions could still be obtained. Ov.Pe xenografts were least sensitive to radioimmunotherapy. The 2 injections of 500 microCi 131I-control MAb gave only transient growth inhibition of OVCAR-3 and Ov.Pe tumors, but gave complete regressions of Ov.Ri(C) xenografts. Biodistribution using tracer doses of 131I-MAb 139H2 and 125I-control MAb showed different degrees of specificity for MAb 139H2 in the 3 xenografts. Radiation doses absorbed in OV.Ri(C), OVCAR-3 and Ov.Pe xenografts per 10 microCi injected dose were 30, 41 and 29 cGy respectively. Treatment with 10 Gy external-beam radiation suggested that the effects of radioimmunotherapy in each tumor line were related to the intrinsic radiosensitivity of the xenografts.
Molthoff
C F
CF
Free University Hospital, Department of Oncology, Amsterdam, The Netherlands.
Pinedo
H M
HM
Schlüper
H M
HM
Rutgers
D H
DH
Boven
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D002945:Cisplatin / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D018396:Mucin-1; D003520:Cyclophosphamide; D002945:Cisplatin