Applications of monoclonal antibodies in the investigation, diagnosis, and treatment of retinoblastoma

Abstract

Monoclonal antibodies have had mixed fortunes since coming to the attention of the research and medical communities; disappointment at their failure to live up to early expectations has often obscured their real value. Understanding, and in some cases overcoming, their limitations has prompted a revival in interest based on their realistic potential. Regulation of malignant characteristics, such as proliferation and dissemination, is a highly complex process involving interchange between growth factors and membrane bound receptors, cellular and matrix interactions, and enzyme mediated remodelling of the interstitial environment in favour ofgrowth and invasion. There is likely to be increasing interest in immunohistochemical and western blot analyses of specific markers of malignancy, leading to greater understanding of tumour progression and metastasis, and antibody interactions may even provide means of modulating these processes. For example, we are currently engaged in a western blot evaluation of NCAM expression in retinoblastoma, and results indicate a link between tumour expression of low binding affinity embryonic type NCAMs and metastatic potential (unpublished data). Progress in the therapeutic uses of monoclonal antibodies in retinoblastoma depend to a large extent on advances made in treating other malignancies, as it is only when clear benefits are demonstrable, in terms of patient survival and morbidity, that current low risk strategies will be abandoned. It is likely, therefore, that some of the prospective therapies, aimed at overcoming the limitations of inadequate specificity, inappropriate toxicity, and poor reagent localisation shall in time be applied to retinoblastoma. Although the potential for tumour spread leads to prophylactic use of enucleation in developed countries, metastatic retinoblastoma is still regarded as a Third World problem. For this reason potential therapy aimed at controlling disseminated disease should be both inexpensive and readily portable for access to outlying regions. Providing cold storage facilities are available, monoclonal antibody conjugates are eminently portable; nevertheless, they are also extremely expensive to produce, limiting their use in circumstances in which there are great demands on meagre health care budgets. It is very important, therefore, to look into cheap and efficient new methods of production, such as prokaryote expression systems, in order to broaden their application in both the laboratory and the clinic. Furthermore, reagents and methodologies should be standardised so as to minimise requirement for expensive specialised equipment or training of personnel.