Section Review: Oncologic, Endocrine and Metabolic: Antibodies as immunogens for cancer therapy

Abstract

The immune response to a monoclonal antibody is viewed as a problem for the use of that antibody as a tumour targeting agent. However, there are several systems in which immune responses to anti-tumour antibody appear to correlate with a better prognosis. Recognition of anti-tumour antibody could stimulate an immunological network, generating anti-idiotypic antibodies which recognise the binding site of anti-tumour antibody (which may therefore represent an ‘internal image’ of the corresponding tumour antigen) that then in turn stimulate anti-tumour responses. The nature of this image may be subtle and complex, with the ability to stimulate cellular immunity as well as being recognised by antibody. Anti-idiotypic antibodies mimicking tumour associated targets are now being evaluated as immunogens in clinical studies. Our own work with a human monoclonal anti-idiotypic antibody shows that cellular immune responses may be activated by anti-idiotypic immunisation; antitumour or anti-idiotypic antibodies were not detectable, and there was no associated toxicity. There was also an apparent survival benefit in immunised patients, which is currently being confirmed in a double blind randomised clinical trial. The molecular and immunological basis of these promising clinical findings depends on the mechanism of T-cell recognition primed by anti-idiotypic immunisation. Specific T-cell proliferation, and evidence of cytotoxicity against autologous tumour cells indicate that both MHC class II and class I restricted responses are being induced in idiotype immunised patients. Anti-idiotypic antibodies of this type may represent an important class of non-toxic T-cell immunogen.