Targeted therapy, monoclonal antibodies used

Colloidal gold-labeled (strept)avidin can be used as highly sensitive detection reagents for microscopy techniques (Cubie and Norval, 1989) (Chapter 24). Finally, cytotoxic substances coupled to (strept)avidin can be used to direct cell-killing activity toward a tumor-cell-bound, biotinylated monoclonal antibody (or other targeting molecule) for cancer therapy (Hashimoto et al, 1984) (Chapter 21). 

Studies in pre-clinical models with human tumours are often carried out in (immuno)defi-cient mice. However, particularly in the case of monoclonal antibody-directed therapy, it is important to recognize that these models, while useful, frequently over-predict activity and under-predict toxicity because the target antigen is tumour-specific in the animal but only tumour-associated in man. 

Monoclonal antibodies have a significant potential as therapeutic agents because of their ability to bind to specific structures as targets. This principle of targeted therapy results in high clinical efficacy whilst minimizing adverse reactions, and thus increases mAb tolerability and use. 

One very new and powerful area of research is that of monoclonal intrabodies (also called intracellular antibodies), which represent a new class of targeting molecules with potential use in gene therapy. Due to their totally different targets, namely inside a cell, and thus different effector functions, they may have a high potential in the treatment of human diseases [6]. 

Monoclonal antibody therapy (MAT) makes use of all the major features of the immune response. It involves vaccination/ immunization, albeit in experimental animals, to induce the desired specific immune response. It exploits the high specificity, selectivity, and affinity of the antibody CDR toward the target antigen to be recognized, highlighted, inactivated, or eliminated, using the characteristics of the Fc portion of an immunoglobulin to facilitate the means for such inactivation or elimination and for selection of appropriate effector mechanisms. Finally, MAT represents a modern form of serotherapy, in which parenteral administration of whole serum or Ig preparations has been replaced by recombinant antibody molecules of a defined specificity. 

The main opportunity for advanced drag delivery systems in this market is in the area of targeted drag delivery. Current research is focused on the development of carriers such as liposomes and on the use of monoclonal antibodies as targeting agents (see Sections 5.2 and 5.3). The eventual market opportunity is considerable—cancer is still one of the commonest fatal diseases, and some of the most deadly forms are resistant to available therapies. The potential market for effective targeting delivery systems may eventually exceed 5 billion. Whether, and how soon, it achieves this figure will depend on the speed with which successful products come to market. 

---