In the present study, we established a dependable system by which human pre-B- and non-T/non-B-
acute lymphoblastic leukemia (ALL) cells are efficiently transplanted into nude mice; the transplanted
tumors provide a useful model for investigating the efficacy of
antitumor agents in the in vivo
therapy of human
cancer. NALM-6 (a
pre-B-ALL cell line) cells were transplanted under varying conditions as the pre-B-
leukemia cells, whereas REH (a non-T/non-B-ALL cell line) cells were transplanted as the non-T/non-B-
leukemia cells. Under optimal and near optimal conditions, 71 of 101 X-irradiated mice (70%) developed distinct
tumors approximately 2 wk after i.d. inoculation of a mixture of NALM-6 cells and X-irradiated human
fibrosarcoma cells. Under the same conditions, 9 of 11 mice (82%) developed
tumors following i.d. inoculation of REH cells admixed with X-irradiated human
fibrosarcoma cells. Examination of the
tumor tissues demonstrated that the
tumors are of
leukemia origin but not of
fibrosarcoma origin. To demonstrate the usefulness of the present
tumors for investigating the efficacy of
antitumor agents in the in vivo
therapy of human
cancer,
immunotoxins were tested for their specific suppressive activity against growing
tumors of the transplanted NALM-6 cells. To this end,
monoclonal antibodies SN5 and SN6 which define a common ALL
antigen, termed CALLA, and a novel
leukemia-associated
cell surface glycoprotein, termed gp160, respectively, were separately conjugated with the A-chain subunit of
ricin, a plant toxin; CALLA and gp160 are expressed on the cell surface of various human non-T-
leukemia cells including NALM-6 cells. The conjugates of SN5 and SN6 with
ricin A-chain (RA) showed specific activity against the
leukemia cells but not against control cells in an in vitro assay. To investigate their in vivo efficacy in suppressing
tumor growth, nude mice which had been inoculated i.d. with NALM-6 cells 25 days in advance and bore distinct palpable
tumors (5 to 6 mm in diameter) were divided into five groups. One group of mice was nontreated as a control. Each of the remaining four groups of mice was given an injection of one of the following agents: (a) purified control mouse
IgG (
IgG1); (b) purified
antibodies SN5 (
IgG1) and SN6 (
IgG1); (c) control
IgG-RA conjugate; or (d) SN5-RA and SN6-RA.
Tumors in all mice of the first four groups including the untreated group grew continuously, causing the mice to die.(ABSTRACT TRUNCATED AT 400 WORDS)