Hybrid molecules prepared by linking toxins to monoclonal antibodies (MAbs) are cytotoxic to cells bearing the target antigen. The toxin most widely used has been the plant toxin ricin as the toxic component, which inhibits protein synthesis at the ribosome level. Immunotoxins based on membrane-active, hemolytic toxins can be a useful alternative when directed towards antigens which do not mediate internalization, as is the case for most carcinoma antigens. We present an alternative for toxic components using a hemolytic toxin acting at the membrane level, due to its phospholipase activity. The hemolytic toxin (HT), isolated from the sea anemone Stoichactis helianthus, has been conjugated to a MAb directed against carcinoembryonic antigen (CEA), by means of an artificial disulphide bridge. The hybrid alpha CEA-HT exhibits no hemolytic activity unless it is reduced. It is toxic for cells (MDA-MB-134) expressing CEA and not toxic for cells (MDA-MB-231) not bearing CEA. An excess of free antibody reverses toxicity.

Hybrid molecules built by conjugation between monoclonal antibodies (MAbs) and toxins are currently being experimentally tested as potential new anti-cancer agents. These immunotoxins have mainly used the plant toxin ricin as the toxic component, which inhibits protein synthesis at the ribosome level. We present an alternative for toxic components using a hemolytic toxin acting at the membrane level, due to its phospholipase activity. The hemolytic toxin (HT), isolated from the sea anemone Stoichactis helianthus, has been conjugated to an antibody towards an antigen expressed on immature T lymphocytes (IOR-T6), by means of an artificial disulphide bridge. The hybrid IOR-T6-HT exhibits no hemolytic activity unless it is reduced. It is toxic for cells (CEM) expressing the IOR-T6 antigen and non-toxic for cells (K562) not bearing the antigen. An excess of unconjugated antibody reverses the toxicity. Immunotoxins based on membrane-active, hemolytic toxins can be a useful alternative when directed towards antigens which do not mediate internalization, as is the case for most carcinoma antigens.

The intracellular distribution of 67Ga was studied in solid hepatoma 22 implanted in C3Ha/6 mice and in normal liver tissue from the same animals at different time intervals. The tissues were fractionated according to differential centrifugation principles, and subcellular fractions were isolated consecutively. The enzyme activities and the accumulation of 67Ga were determined in each fraction. The subcellular distribution of 67Ga in the tumor tissue was different compared with normal liver; in tumor it was found mainly in the nuclear fraction and this distribution was independent of time, but in normal liver the accumulation was mainly in the mitochondrial fraction, this was time-dependent and the maximal uptake was found 48 h after 67Ga administration.

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