Chimeric toxins in cancer treatment

Abstract

A chimeric toxin is composed of a protein toxin connected to a binding ligand such as an antibody or growth factor. Chimeric toxins include conventional immunotoxins, in which the ligand is an antibody, growth-factor fusion toxins, in which the growth factor ligand is fused in single-chain fashion to the toxin, and recombinant immunotoxins, in which the Fv fragment of an antibody is fused to the toxin. Toxins kill cells by catalytic inhibition of protein synthesis within the cell cytosol, and are targeted to cells displaying internalising receptors for the ligand. Chimeric toxins have recently been tested clinically in solid tumours expressing the Le^Y antigen, the transferrin receptor, and the IL-4 receptor, and in haematologic malignancies expressing CD22, CD19, high affinity IL-2 receptors and CD25. Several chimeric toxins have demonstrated potent clinical efficacy in patients with malignant disease refractory to surgery, radiation therapy and chemotherapy, the traditional modalities of cancer treatment. Chimeric toxins are evolving into a separate modality of cancer treatment, which rationally targets cells based on surface markers. Impediments to clinical efficacy include immunogenicity, toxicity to normal antigen positive or negative tissues, and limited penetration of solid masses of tumour.

• diphtheria toxin
• disulphide-stabilised
• fusion protein
• fv
• growth factor
• immunotoxins
• interleukin
• monoclonal antibody
• Pseudomonas exotoxin
• saporin