Leukemic cell targeting and therapy by monoclonal antibody in a mouse model system.
Academic Article
Overview
abstract
A monoclonal antibody prepared against the Rauscher virus envelope glycoprotein with a molecular weight of 70,000 targeted to neoplastic cells and cured the Rauscher leukemia virus-induced erythroleukemia in BALB/c mice. This antibody, 103A, specifically reacted with the Rauscher and Friend erythroleukemia viruses and erythroleukemic cells but did not react with other murine ecotropic or xenotropic viruses or feline leukemia virus or with normal spleen cells, thymocytes, or fibroblasts, as measured by radioimmunoassays. P3, a control antibody of the same immunoglobulin G1 subclass, did not bind to any of these cells or viruses. This specificity was maintained in vivo. 125I-Labelled 103A injected into mice targeted to leukemic spleen cells but not to normal cells. Mean uptake ratios of binding to leukemic over normal spleen cells ranged from greater than 70 at 7 hr after injection to less than 10 at 40 hr later. The control antibody showed no binding in vivo. A single small dose of 103A was able to cure leukemic mice as assayed by spleen focus formation on Day 8 or splenomegaly on Day 20. The 50% effective dose was 1.5 micrograms when injected 72 hr after onset of leukemia. The therapeutic potencies of drugs, toxins, and cytotoxic radioisotopes conjugated to antibodies can be quantitatively compared using the established dose-response curve. Such quantitative comparisons showed that 131-labeled 103A immunoglobulin G was no more potent than unlabeled 103A immunoglobulin G in this system.
