Cell-targeting fusion constructs containing recombinant gelonin

Methods Enzymol. 2012:502:167-214. doi: 10.1016/B978-0-12-416039-2.00008-2.

Abstract

Therapeutic agents capable of targeting tumor cells present as established tumors and micrometastases have already demonstrated their potential in clinical trials. Immunotoxins targeting hematological malignancies and solid tumors have additionally demonstrated excellent clinical activity. This review focuses on our design and characterization studies of constructs composed of recombinant gelonin toxin fused to either growth factors or single-chain antibodies targeting solid tumor cells, tumor vasculature or hematological malignancies. These agents demonstrate cytotoxicity at nanomolar or sub-nanomolar levels. All of these constructs display impressive selectivity and specificity for antigen-bearing target cells in vitro and in vivo and are excellent clinical trial candidates.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / immunology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply*
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / metabolism
  • Epitopes
  • Humans
  • Immunoglobulin Fragments / genetics
  • Immunoglobulin Fragments / immunology*
  • Immunoglobulin Fragments / pharmacology
  • Immunotoxins / genetics
  • Immunotoxins / immunology*
  • Immunotoxins / pharmacology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neovascularization, Pathologic*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology
  • Ribosome Inactivating Proteins, Type 1 / genetics
  • Ribosome Inactivating Proteins, Type 1 / immunology*
  • Ribosome Inactivating Proteins, Type 1 / pharmacology
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology*
  • Single-Chain Antibodies / pharmacology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Epitopes
  • Immunoglobulin Fragments
  • Immunotoxins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Fusion Proteins
  • Ribosome Inactivating Proteins, Type 1
  • Single-Chain Antibodies
  • GEL protein, Gelonium multiflorum