Immunotoxins: new therapeutic reagents for autoimmunity, cancer, and AIDS

Immunotoxins consist of cell-reactive ligands coupled to toxins or their toxic subunits. The ligands are usually antibodies, hormones, or growth factors and the toxins are of bacterial or plant origin. In vitro studies using A chain-containing immunotoxins specifically to kill tumor cells were successful and led to further experiments in vivo. Such studies, carried out over the past 5 years in both animals and humans, have demonstrated that the efficacy of immunotoxins in vivo is often poor, due to problems involving instability of the conjugate, inferior potency, inaccessibility of tumor cells, nonspecific binding to cells other than the target cells, and survival of antigen-negative mutants. In addition, immune responses against both the ligand and the A chain are usually elicited, precluding repeated therapy. During the past several years, there have been attempts to solve these problems and develop more effective immunotoxins.