Extravascular Diffusion and Convection of Antibodies in Tumors

With the advent of hybridoma technology came the ability to prepare large volumes of monoclonal antibody (McAb). (In this presentation the McAb referred to is usually of immunoglobulin G. For work with antibody fragments see references: Buchegger et al (1986), Buraggi et al (1985), Carrasquillo et al, 1984), Covell et al (1986), Harwood et al (1985), Mach et al (1980), Mach et al (1983), Wahl et al (1983)). Antibody could be prepared which was specific for antigens that were at a higher concentration in tumors than in other tissues, so called tumor-associated antigens (TAAs), Only rarely are McAbs cytotoxic in their own right and to have an effect on tumors it is usually necessary to attach a cytotoxin. Cytotoxins may need to be delivered either to the surface of each and every tumor cell (drugs, plant toxins) (Baldwin, 1985; Thorpe, 1985) or simply into the general tumor area (radionuclides, enzymes for activating pro-drugs) (Epenetos et al, 1987; Humm and Cobb, 1990; Bagshawe, 1988; Cobb and Humm, 1986). It is clearly important to know the likely intratumor distribution of any injected antibody down to the microscopic level if we wish to assess whether the cytotoxin-carrying antibody is likely to be effective. Our work on this problem has been predominantly carried out on slow-growing animal tumors, using I-125-labelled McAbs to TAAs. The animals are sacrificed at intervals after McAb injection and the histological distribution of McAb in relation to the target cell studied using auto-radiography. In an attempt to “bridge the gap” between the experimental animal tumor data and the situation in patients we have also studied the distribution of the host’s own antibody using frozen sections of human tumors together with immunoperoxidase staining for immunoglobulin.