Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models
In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.
- Research Organization:
- New York State Dept. of Health, Buffalo
- OSTI ID:
- 5591900
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:10
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
FIBROSARCOMAS
IMMUNOTHERAPY
IMMUNOSUPPRESSION
RADIOINDUCTION
MONOCLONAL ANTIBODIES
RADIOIMMUNOASSAY
BIOLOGICAL MODELS
GROWTH
HISTOLOGY
IN VIVO
INHIBITION
IODINE 125
LEUKEMIA
MAN
MICE
TOXINS
TRITIUM COMPOUNDS
TUMOR CELLS
X RADIATION
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
HEMIC DISEASES
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
IONIZING RADIATIONS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
PRIMATES
RADIATIONS
RADIOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
RODENTS
SARCOMAS
THERAPY
TOXIC MATERIALS
TRACER TECHNIQUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals
550301 - Cytology- Tracer Techniques