We have analysed the specificity of monoclonal antibodies to human leucocyte subsets by three methods. The distribution of antigen bearing cells has been studied in frozen tissue sections of lymphoid and other tissues by immunofluorescence or immunoenzymatic methods. The cellular distribution of antigen has been compared with existing well established markers and the function of antigen bearing cells has been studied by separation and assay in in vitro model systems. Antibodies characterised in this way may yield useful information when applied to clinical problems.

When bone marrow (BM) is taken, cells in suspension are accessible to antibodies. BM transplantation is therefore an ideal situation for using monoclonal antibodies in therapy. These applications include prevention of graft versus host disease by eliminating T cells from allogeneic BM marrow, and the elimination of residual malignant cells from autologous bone marrow. Me Ab-s are currently tested for the removal of residual leukaemic cells in the common form of acute lymphoblastic leukaemia (ALL) and in thymic ALL. Encouraging experiments also indicate that the removal of B leukaemias/lymphomas from the BM will also be feasible.

The review summarises the various ways Ab-s can damage coated ‘unwanted’ cells (opsonisation, complement mediated lysis, and Ab-s coupled to toxins), and the principles for selecting Me Ab-s for BM transplantation.

By the late 1970s it had become clear that the immunosuppressive effects of conventional anti lymphocyte serum (ALS) were mediated by only a small component of the anti lymphocyte antibodies present. This fact meant that attempts to improve the safety, potency and standardisation of conventional ALS by raising xenosera to single, purified lymphocyte antigens were faced with considerable technical and theoretical problems. Coincidentally and very fortunately, it was at this time that the potential of monoclonal antibodies in the field of ALS were becoming obvious. Their advent has dramatically transformed the situation, from a bleak one with few prospects to one where the early promise of ALS is likely to be realised in the clinic within the next few years. This review looks at why it is that monoclonal antibodies have so changed the situation, and then discusses in detail the optimal properties, in terms of specificity and other characteristics, of immunosuppressive monoclonal antibodies, and finally looks at precisely how they should be used in the clinic.

The production of monoclonal antibodies specifying tumour associated antigens is illustrated by studies with a spontaneously arising rat mammary carcinoma (Sp4). Fusion of spleen cells from tumour-immune rats with mouse myeloma (P3NS1) yielded hybridomas secreting antibody reacting with a tumour specific antigen. These approaches have subsequently been used to produce monoclonal antibodies reacting with human osteogenic sarcoma, although in this case the antigens detected are tumour associated rather than tumour-specific.

The diagnostic applications of these monoclonal antibodies have been explored particularly to evaluate whether radiolabelled preparations can be used for ‘imaging’ tumours. This approach has been validated with the human osteogenic sarcoma xenograft in tests showing that tumours can be detected by y-camera scanning following injection of 131I-labelled antibody when used in conjunction with blood pool labelling using 113MIn and a computerised subtraction technique.

Monoclonal antibodies also have considerable potential for targetting drugs. These approaches are illustrated by studies using anti-rat mammary carcinoma Sp4 monoclonal antibody linked to adriamycin for therapy of subcutaneous tumour. In addition to drug conjugates, monoclonal antibodies are being used for targeting immunomodulating agents. This is illustrated by another series of studies in which the anti-human osteogenic sarcoma monoclonal antibody has been conjugated to human lymphoblastoid cell interferon to produce a reagent for activating host natural killer cells.

Current research into viral monoclonal antibodies is reviewed in the light of their use or potential use as diagnostic reagents. Special attention is paid to influenza, the adenovirus group, herpes virus hominis types 1 and 2, rota viruses, hepatitis and cytomegalovirus. Although monoclonal antibodies have many advantages, particularly as regards specificity, purity, reproducibility, homogeneity and availability in unlimited supplies, certain problems are inherent in their very nature. Their preciseness may in fact be a hindrance to their use in diagnosis necessitating their recombination in pools and the quality assessment of their reactions with their homologous 'wild" types presents large logistic problems. There is no doubt that a powerful new serological tool has become available but their large-scale diagnostic use may be a little premature.

Immunoassays have markedly enlarged the armamentarium of the clinical chemist during the last twenty years. Radioimmunoassays and their variants, in particular, now provide evidence which is central to diagnosis and patient management in endocrinology and certain other disorders. Currently used methods employ labelled antigens in the radioimmunoassay (RIA) method first described for insulin by Yalow and Berson. The advent of monoclonal antibodies seems to remove the one major barrier to the use of methods based upon labelled antibodies–the immunoradiometric (IRMA) method as proposed by Miles and Hales. These procedures offer advantages of speed, sensitivity, working range, specificity and robustness which strongly suggest that they will replace RIA for the microdetermination of specific proteins. Nevertheless, their specificity is based upon the recognition of a single epitope on the antigen and thorough testing on varied patient material will be required before they can safely be adopted for routine use.