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Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments.

Abstract
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.
AuthorsF Buchegger, C Pfister, K Fournier, F Prevel, M Schreyer, S Carrel, J P Mach
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 83 Issue 5 Pg. 1449-56 (May 1989) ISSN: 0021-9738 [Print] United States
PMID2708519 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Immunoglobulin Fab Fragments
  • Iodine Radioisotopes
Topics
  • Animals
  • Antibodies, Monoclonal (administration & dosage, therapeutic use, toxicity)
  • Carcinoembryonic Antigen (immunology)
  • Carcinoma (pathology, therapy)
  • Colonic Neoplasms (pathology, therapy)
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Fibrosis
  • Immunoglobulin Fab Fragments (administration & dosage)
  • Iodine Radioisotopes (administration & dosage)
  • Male
  • Mice
  • Mice, Nude
  • Quality Control
  • Remission Induction

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