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Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments.
Buchegger, F; Pfister, C; Fournier, K; Prevel, F; Schreyer, M; Carrel, S; Mach, J P.
Afiliación
  • Buchegger F; Ludwig Institute for Cancer Research, Lausanne Branch, Switzerland.
J Clin Invest ; 83(5): 1449-56, 1989 May.
Article en En | MEDLINE | ID: mdl-2708519
Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation. The results demonstrate the selective destruction of established human colon carcinoma transplants by intravenous injection of either single or fractionated doses of 131I-MAb F(ab')2.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fragmentos Fab de Inmunoglobulinas / Carcinoma / Antígeno Carcinoembrionario / Neoplasias del Colon / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: J Clin Invest Año: 1989 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fragmentos Fab de Inmunoglobulinas / Carcinoma / Antígeno Carcinoembrionario / Neoplasias del Colon / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: J Clin Invest Año: 1989 Tipo del documento: Article País de afiliación: Suiza