Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin

M. J. Glennie, H. M. McBride, F. Stirpe, P. E. Thorpe, A. T. Worth, G. T. Stevenson

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The potency and specificity of immunotoxins consisting of monoclonal antiidiotype conjugated to the ribosome-inactivating protein, saporin, have been evaluated in the treatment of guinea pig L2C B lymphocytic leukemia. The immunotoxins were therapeutically much more effective than their parent antibodies. Their specificity reflected that of their antiidiotype component. Although the leukemia emerged eventually in most animals treated with these conjugates, most of the cells showed altered Ig expression, which rendered them resistant to the therapy. Commonly, the emerging cells had lost μ heavy chain production, leaving them negative for intracellular, surface, and secreted IgM, but still positive for λ light chain production. In addition, a minor group of L2C variants was identified in a protocol designed to detect mutants at very low frequency: here the cells were exposed in vitro to immunotoxin and, while still viable as judged by dye-exclusion, inoculated in large numbers into animals. In tumor that emerged under these circumstances, the majority of cells were again immunoglobulin-negative; however a minority exhibited IgM with an altered idiotype (Idiotope-loss variants), rendering them unreactive with immunotoxin. Immunotherapy with unmodified anti-Id antibody alone does not reveal these variants, and we suggest it is the increased selective force exerted by the highly potent immunotoxins that allow these minor nonreactive populations to emerge.

Original languageEnglish (US)
Pages (from-to)43-62
Number of pages20
JournalJournal of Experimental Medicine
Volume166
Issue number1
DOIs
StatePublished - 1987

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B-Cell Leukemia
Immunotoxins
Immunoglobulins
Antibodies
Immunoglobulin M
Ribosome Inactivating Proteins
Therapeutics
Immunotherapy
Anti-Idiotypic Antibodies
Guinea Pigs
Leukemia
Coloring Agents
saporin
Light
Population
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin. / Glennie, M. J.; McBride, H. M.; Stirpe, F.; Thorpe, P. E.; Worth, A. T.; Stevenson, G. T.

In: Journal of Experimental Medicine, Vol. 166, No. 1, 1987, p. 43-62.

Research output: Contribution to journalArticle

Glennie, M. J. ; McBride, H. M. ; Stirpe, F. ; Thorpe, P. E. ; Worth, A. T. ; Stevenson, G. T. / Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin. In: Journal of Experimental Medicine. 1987 ; Vol. 166, No. 1. pp. 43-62.
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