Bispecific anti-CD22/anti-CD3-ricin A chain immunotoxin is cytotoxic to Daudi lymphoma cells but not T cells in vitro and shows both A-chain-mediated and LAK-T-mediated killing

Guo Liang Shen, Jia Ling Li, Ellen S. Vitetta

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13 Scopus citations

Abstract

We have generated a bispecific anti-CD22/anti-CD3 immunotoxin (IT) and determined whether it would exert both lymphokine-activated killer (LAK) T cell-mediated and ricin A chain (dgA)-mediated toxicity to Daudi tumor cells but not to T cells in vitro. One parental IT, Fab'-anti-CD22-dgA makes a potent immunotoxin for B cells, but not T cells, while the other, Fab'-anti- CD3-dgA, kills neither T nor B cells. Three mouse quadromas were generated and the bispecific Abs (BsAbs) were purified by double affinity chromatography. Two of the three purified BsAbs induced significant proliferation and IL-2 production in T cells. All three BsAbs induced LAK-T cell-mediated specific lysis of CD22+ Daudi cells. Two of the purified Ab were conjugated to dgA. Using a 51Cr release assay in the presence of LAK- T cells and Daudi target cells, the IC50s of the BsAbs were 3.5 x 10-10 M and 9 x 10-11 M, as compared to 2.1 x 10-11 M and 3.2 x 10-11 M, for their respective ITs. Hence, in the presence of LAK-T cells, the BsITs were 3- to 17-fold more cytotoxic than unconjugated BsAbs in 51Cr-release assays. Daudi cells were also treated in vitro with different mixtures of LAK-T cells, BsAbs, and BsITs and then adoptively transferred into SCID mice. As determined by the mean paralysis time of the recipients, in the presence of LAK-T cells the BsITs had impressive anti-tumor activity.

Original languageEnglish (US)
Pages (from-to)2368-2376
Number of pages9
JournalJournal of Immunology
Volume152
Issue number5
StatePublished - Mar 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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