Effects of monoclonal antibodies that block transferrin receptor function on the in vivo growth of a syngeneic murine leukemia.

摘要: The ability of monoclonal antibodies (MAbs) against the murine transferrin receptor to inhibit growth transplanted syngeneic AKR/J SL-2 leukemic cells has been investigated. Two rat IgM antibodies, RI7 208 and REM 17.2, which both block function, inhibited in vitro at concentrations 5–10 µg per ml. However, was more effective than 17.2 prolonging survival tumor-bearing mice. antitumor effects MAb were dependent on antibody dose number inoculated. serum clearance [75Se]methionine-labeled similar consisted an initial rapid phase over first 2 days followed by a slower phase. A single mg maintained concentration (>10 µg/ml) sufficient cell for 2–3 days. liver, kidney, spleen major sites each accumulated regardless whether trace or saturating amounts administered. specific activity found s.c. tumors about 2-fold less that liver. It shown multiple doses administered schedule aimed maintaining therapeutic level 1–3 weeks dose. Further, administration MAb, combination with anti-Thy-1.1 19E12, either alone. mutant selected resistant inhibitory . these vivo suggests mechanism inhibits tumor is directly blocking function. Acute toxicity associated minimal. assays myeloid erythroid colony-forming units bone marrow mice given showed depression stem elevated numbers cellular spleen.