In vivo therapy of the BCL1 tumor: Effect of immunotoxin valency and deglycosylation of the ricin A chain

R. J. Fulton, J. W. Uhr, E. S. Vitetta

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Abstract

The in vivo therapeutic effects of Fab' and IgG anti-δ (anti-IgD)-ricin A chain immunotoxins were compared in mice bearing the surface IgD-positive BCL1 leukemia. The immunotoxins were prepared with either native or deglycosylated ricin A chain. Immunotoxin therapy was assessed both by the number of cells bearing the BCL1 immunoglobulin idiotype which remained in the spleen 24-48 h after injection with immunotoxin and by adoptive transfer of these spleen cells into normal mice. Immunotoxins prepared with either Fab'-anti-δ or IgG-anti-δ and native A chain induced a dose-dependent reduction in the number of idiotype-positive BCL1 cells present in the spleens of the tumor-bearing mice. The maximal therapeutic response was achieved with 250 μg of immunotoxin (containing 80-100 μg A chain) per mouse for both immunotoxins, resulting in tumor reduction of approximately 90%. This represents an elimination of 3-4 x 108 tumor cells. Reduction in the number of tumor cells was not observed with control reagents including antibody alone, antibody mixed with A chain, or an immunotoxin of irrelevant specificity. A Fab' immunotoxin prepared with deglycosylated ricin A chain was approximately 5-fold more effective as an antitumor reagent than the same immunotoxin prepared with native A chain; thus, optimal therapy was achieved after injection of 50 μg of immunotoxin (containing 15-20 μg A chain). Since the immunotoxins prepared with deglycosylated A chain were only 2-3-fold more toxic to the mice than those prepared with native A chain, the former resulted in a 2-3-fold increase in the therapeutic index.

Original languageEnglish (US)
Pages (from-to)2626-2631
Number of pages6
JournalCancer Research
Volume48
Issue number9
StatePublished - 1988

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Ricin
Immunotoxins
Neoplasms
Therapeutics
Spleen
Immunoglobulin Idiotypes
Cell Count
Immunoglobulin D
Injections
Adoptive Transfer
Antibodies
Poisons
Therapeutic Uses
Leukemia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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In vivo therapy of the BCL1 tumor : Effect of immunotoxin valency and deglycosylation of the ricin A chain. / Fulton, R. J.; Uhr, J. W.; Vitetta, E. S.

In: Cancer Research, Vol. 48, No. 9, 1988, p. 2626-2631.

Research output: Contribution to journalArticle

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abstract = "The in vivo therapeutic effects of Fab' and IgG anti-δ (anti-IgD)-ricin A chain immunotoxins were compared in mice bearing the surface IgD-positive BCL1 leukemia. The immunotoxins were prepared with either native or deglycosylated ricin A chain. Immunotoxin therapy was assessed both by the number of cells bearing the BCL1 immunoglobulin idiotype which remained in the spleen 24-48 h after injection with immunotoxin and by adoptive transfer of these spleen cells into normal mice. Immunotoxins prepared with either Fab'-anti-δ or IgG-anti-δ and native A chain induced a dose-dependent reduction in the number of idiotype-positive BCL1 cells present in the spleens of the tumor-bearing mice. The maximal therapeutic response was achieved with 250 μg of immunotoxin (containing 80-100 μg A chain) per mouse for both immunotoxins, resulting in tumor reduction of approximately 90{\%}. This represents an elimination of 3-4 x 108 tumor cells. Reduction in the number of tumor cells was not observed with control reagents including antibody alone, antibody mixed with A chain, or an immunotoxin of irrelevant specificity. A Fab' immunotoxin prepared with deglycosylated ricin A chain was approximately 5-fold more effective as an antitumor reagent than the same immunotoxin prepared with native A chain; thus, optimal therapy was achieved after injection of 50 μg of immunotoxin (containing 15-20 μg A chain). Since the immunotoxins prepared with deglycosylated A chain were only 2-3-fold more toxic to the mice than those prepared with native A chain, the former resulted in a 2-3-fold increase in the therapeutic index.",
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