Monoclonal antibodies coupled to drugs and toxic agents (
immunotoxins) or
radionuclides (
radioimmunoconjugates) represent new tools for
immunotherapy of haematological
malignancies.
Immunotoxins constructed with toxins of either plant or bacterial origin have shown a powerful antitumor activity both in vitro and in mice with
severe combined immunodeficiency bearing various kinds of leukaemias and
lymphomas. Preliminary clinical trials have shown an activity of these compounds at least in a proportion of patients. However, tumour responses have generally been partial and transient. The main problems with
immunotoxin therapy remain the inability of
immunotoxins to target tumour cells in the presence of a high burden of disease, the host immune response against both the antibody and the toxin moieties, which precludes repeated administration of
immunotoxins, and the vascular leak syndrome. Targeting of tumour cells with specific
antibodies armed with
radionuclides (usually
iodine-131 or
yttrium-90) appears to be an even more attractive approach. Preliminary clinical studies have clearly demonstrated the ability of
radioimmunoconjugates, especially when administered at high dose followed by bone marrow rescue, to induce durable complete remission in patients with non-Hodgkin's
lymphomas refractory to conventional
therapies.
Radioimmunotherapy also overcomes the antigenic heterogeneity of the tumour cell population, since
antigen negative tumour cells will be irradiated by the nearby targeted
antigen-positive cells. Efforts should now be focused on defining more precisely the optimal clinical setting for administration of
immunotoxin and
radioimmunoconjugates (e.g.
minimal residual disease), to reduce the immunogenicity of these compounds and solve the problem of vascular leak syndrome.