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In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain.
Cancer Res. 1988 May 01; 48(9):2626-31.CR

Abstract

The in vivo therapeutic effects of Fab' and IgG anti-delta (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-delta or IgG-anti-delta 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 micrograms of immunotoxin (containing 80-100 micrograms A chain) per mouse for both immunotoxins, resulting in tumor reduction of approximately 90%. This represents an elimination of 3-4 X 10(8) 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 micrograms of immunotoxin (containing 15-20 micrograms 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.

Authors+Show Affiliations

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3258547

Citation

Fulton, R J., et al. "In Vivo Therapy of the BCL1 Tumor: Effect of Immunotoxin Valency and Deglycosylation of the Ricin a Chain." Cancer Research, vol. 48, no. 9, 1988, pp. 2626-31.
Fulton RJ, Uhr JW, Vitetta ES. In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. Cancer Res. 1988;48(9):2626-31.
Fulton, R. J., Uhr, J. W., & Vitetta, E. S. (1988). In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. Cancer Research, 48(9), 2626-31.
Fulton RJ, Uhr JW, Vitetta ES. In Vivo Therapy of the BCL1 Tumor: Effect of Immunotoxin Valency and Deglycosylation of the Ricin a Chain. Cancer Res. 1988 May 1;48(9):2626-31. PubMed PMID: 3258547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo therapy of the BCL1 tumor: effect of immunotoxin valency and deglycosylation of the ricin A chain. AU - Fulton,R J, AU - Uhr,J W, AU - Vitetta,E S, PY - 1988/5/1/pubmed PY - 1988/5/1/medline PY - 1988/5/1/entrez SP - 2626 EP - 31 JF - Cancer research JO - Cancer Res VL - 48 IS - 9 N2 - The in vivo therapeutic effects of Fab' and IgG anti-delta (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-delta or IgG-anti-delta 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 micrograms of immunotoxin (containing 80-100 micrograms A chain) per mouse for both immunotoxins, resulting in tumor reduction of approximately 90%. This represents an elimination of 3-4 X 10(8) 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 micrograms of immunotoxin (containing 15-20 micrograms 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/3258547/In_vivo_therapy_of_the_BCL1_tumor:_effect_of_immunotoxin_valency_and_deglycosylation_of_the_ricin_A_chain_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=3258547 DB - PRIME DP - Unbound Medicine ER -