Immunotoxins containing saporin 6 and monoclonal antibodies recognizing plasma cell-associated antigens: effects on target cells and on normal myeloid precursors (CFU-GM)

Eur J Haematol. 1989 Mar;42(3):238-45. doi: 10.1111/j.1600-0609.1989.tb00105.x.

Abstract

Monoclonal antibodies 8A and 62B1, recognizing plasma cell-associated antigens, were covalently linked to saporin 6, a ribosome-inactivating protein similar to the A-chain of ricin. Both immunotoxins were tested on target human cell lines U266 and Raji, on non-target K562 cell line and on myeloid CFU-GM progenitors. The cloning efficiency and viability of target cells were strongly reduced by 8A-saporin 6 and 62B1-saporin 6 immunotoxins, with an ID50 up to 200,000-fold lower than free saporin 6, whilst the K562 non-target cell line was unaffected. Normal human myeloid precursors (CFU-GM) were inhibited by immunotoxins only to a limited extent. An application of this model for autologous bone marrow transplantation in multiple myeloma patients is proposed. Since no eradication of cloning target cells was achieved by a single immunotoxin, mixtures made with different antibodies could help to reach this goal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Colony-Forming Units Assay
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Immunoglobulin G
  • Immunotoxins / pharmacology*
  • Mice
  • N-Glycosyl Hydrolases*
  • Plant Proteins / pharmacology*
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Tumor Cells, Cultured / drug effects*

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, B-Lymphocyte
  • Antineoplastic Agents, Phytogenic
  • Immunoglobulin G
  • Immunotoxins
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • N-Glycosyl Hydrolases
  • Saporins