PMID- 1530766 OWN - NLM STAT- MEDLINE DCOM- 19920117 LR - 20131121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 52 IP - 1 DP - 1992 Jan 1 TI - Antitumor effect of 2'-deoxy-5-fluorouridine conjugates against a murine thymoma and colon carcinoma xenografts. PG - 132-7 AB - The conjugation of antineoplastic drugs to monoclonal antibodies reactive with tumor associated antigens conveys selective cytotoxicity, overcoming the systemic toxicities caused by drugs during standard chemotherapy. 2'-Deoxy-5-fluorouridine, a more potent derivative of 5-fluorouracil, is an antimetabolite which exerts its cytotoxic action by inhibiting the enzyme thymidylate synthetase and as a result inhibits DNA synthesis. 2'-Deoxy-5-fluorouridine was successfully conjugated to anti-Ly-2.1 reactive with the murine thymoma ITT(1)75NS E3, I-1, and 250-30.6 reactive with human colon cancer cells using the active ester of 2'-deoxy-5-fluoro-3'-O-succinoyluridine (5FdUrdsucc). In vitro, 5Fd-Urdsucc-anti-Ly-2.1 was selectively cytotoxic against ITT(1)75NS E3 murine thymoma cells at nanomolar concentrations. The human colon carcinoma cell LIM1899 was inhibited by 5FdUrdsucc-I-1 conjugates in the range of 10(-7)-10(-8) M, as were Colo 205 cells by 5FdUrdsucc-250-30.6 conjugates. In vivo, 5FdUrdsucc conjugates were more effective than equivalent amounts of free 5FdUrdsucc. Against the ITT(1)75NS E3 murine thymoma, a single dose of 100 micrograms (5FdUrdsucc equivalents) 5FdUrdsucc-anti-Ly-2.1 resulted in 85% tumor inhibition compared to mean tumor size of control mice. Irrelevant 5FdUrdsucc conjugates failed to inhibit tumor growth. Multiple doses of 5FdUrdsucc-I-1 conjugate produced 50% growth inhibition of the moderately differentiated tumor LIM1899. In contrast, the human colon carcinoma Colo 205 was relatively resistant to free 5FdUrdsucc and 5FdUrdsucc-250-30.6 conjugates. FAU - Krauer, K G AU - Krauer KG AD - Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia. FAU - McKenzie, I F AU - McKenzie IF FAU - Pietersz, G A AU - Pietersz GA LA - eng PT - Journal Article PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Antibodies, Monoclonal) RN - 0 (Immunotoxins) RN - 039LU44I5M (Floxuridine) SB - IM MH - Animals MH - Antibodies, Monoclonal/metabolism/therapeutic use MH - Colonic Neoplasms/metabolism/*therapy MH - Drug Screening Assays, Antitumor MH - Floxuridine/metabolism/*therapeutic use MH - Humans MH - Immunotoxins/metabolism/*therapeutic use MH - Mice MH - Neoplasm Transplantation MH - Thymoma/metabolism/*therapy MH - Thymus Neoplasms/metabolism/*therapy MH - Tumor Cells, Cultured EDAT- 1992/01/01 00:00 MHDA- 1992/01/01 00:01 CRDT- 1992/01/01 00:00 PHST- 1992/01/01 00:00 [pubmed] PHST- 1992/01/01 00:01 [medline] PHST- 1992/01/01 00:00 [entrez] PST - ppublish SO - Cancer Res. 1992 Jan 1;52(1):132-7.