Antibody engineering for targeted therapy of cancer: recombinant Fv-immunotoxins.
Recombinant Fv-immunotoxins are a new class of biologic anticancer agents composed of a recombinant antibody fragment linked to a very potent bacterial toxin. These potent molecules are designed to specifically bind and kill cancer cells that express a specific target antigen on their cell surface. Recombinant Fv-immunotoxins are an excellent example for the concept of rational drug design. They combine the progress in understanding cancer biology, -the recent knowledge on the mechanisms of malignant transformation and the special properties of cancer cells, -with the enormous developments in recombinant DNA technology and antibody engineering. Recombinant Fv immunotoxins were developed for solid tumors and hematological malignancies and have been characterized intensively for their biological activity in vitro and in vivo in animal models. The excellent in vitro and in vivo activities of recombinant Fv-immunotoxins have lead to their pre-clinical development and to the initiation of clinical trial protocols. Recent trials have demonstrated potent clinical efficacy in patients with malignant diseases that are refractory to traditional modalities of cancer treatment. It is thus suggested that this strategy can be developed into a separate modality of cancer treatment with the basic rationale of specifically targeting cancer cells on the basis of their unique surface markers combined with potent effective biological toxic agents that directly kill the cancer cell. Efforts are now being made to improve the current molecules and to develop new agents with better clinical efficacy. In this review, we will describe the rationale in designing Fv-immunotoxins and will review current progress made in using these agents for cancer treatment.
Niv
R
R
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel. reiter@gx.technion.ac.il
Cohen
C J
CJ
Denkberg
G
G
Segal
D
D
Reiter
Y
Y
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage* / Q000235:genetics; D000922:Immunotoxins / Q000008:administration & dosage* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics
D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D011994:Recombinant Proteins