Comparison of131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts

Publisher Website
Google Scholar
Abstract
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. × 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. × 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 μCi 131I‐specific MAb 139H2, administered i.v. × 2 with a 2‐week interval, was more effective than CDDP or CTX. The 500 μCi 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 μ‐Ci 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 μCi 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.