Antibody Engineering for Targeted Therapy of Cancer Recombinant Fv-Immunotoxins

Revital      Niv; Cyril   J.   Cohen; Galit      Denkberg; Dina      Segal; Yoram      Reiter

Abstract

Recombinant Fv-immunotoxins are a new class of biologic anticanceragents composed of a recombinant antibody fragment linked to a very potentbacterial toxin. These potent molecules are designed to specifically bind and killcancer cells that express a specific target antigen on their cell surface. RecombinantFv-immunotoxins are an excellent example for the concept of rational drug design.They combine the progress in understanding cancer biology, -the recentknowledge on the mechanisms of malignant transformation and the specialproperties of cancer cells, -with the enormous developments in recombinant DNA technology and antibodyengineering. Recombinant Fv immunotoxins were developed for solid tumors and hematological malignancies and havebeen characterized intensively for their biological activity in vitro and in vivo in animal models. The excellentin vitro and in vivo activities of recombinant Fv-immunotoxins have lead to their pre-clinical developmentand to the initiation of clinical trial protocols.Re cent trials have demonstrated potent clinical efficacy in patients with malignant diseases that are refractoryto traditional modalities of cancer treatment.It is thus suggested that this strategy can be developed into a separate modality of cancer treatment with thebasic rationale of specifically targeting cancer cells on the basis of their unique surface markers combined withpotent effective biological toxic agents that directly kill the cancer cell. Efforts are now being made to improvethe 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 forcancer treatment.

Keywords: Antibody Engineering, Targeted Therapy, Cancer, Recombinant Fv-Immunotoxins, Anticancer Agents, recombinant DNA technology, bacterial toxin, drug design, Immunotherapy