Antibodies and vaccines--hope or illusion?

The search for target molecules on tumor cells eliciting strong immune responses in cancer patients has been pursued over decades. Growth factors and their respective receptors were discovered as suitable targets for passive or active immunotherapy approaches. Monoclonal antibodies directed against some of these targets like the proto-oncogene HER2/neu have become an accepted standard of therapy in the clinical management of subgroups of HER2/neu overexpressing breast cancer patients and in other malignancies. Antibodies against multiple other target molecules like epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), etc., are explored in ongoing trials in order to enter clinical practice in the near future. More recently, potent techniques have been developed to identify cancer antigens eliciting spontaneous immune responses in cancer patients. Cancer vaccination strategies targeting some of these cancer antigens have also been developed, and are maturing for clinical application. With reliable immunomonitoring techniques in place it has been shown that vaccination with some of these cancer antigens may induce strong integrated (humoral and cellular) immune responses in antigen-positive cancer patients. A prominent example is the cancer testis (CT-) antigen NY-ESO-1, which is expressed in 30% of all breast cancers. NY-ESO-1 is one of the most immunogenic human cancer antigens known to date. The aim of ongoing clinical trials is to induce or augment preexisting immune responses in cancer patients with strong NY-ESO-1 positive disease. There is preliminary evidence that patients with strong NY-ESO-1-specific immune responses have more favorable courses of disease. In several clinical phase I trials targeting HER2/neu it was shown that antigen-specific T cell responses could be induced. Another new cancer antigen explored for cancer vaccination is the breast differentiation antigen NY-BR-1, expressed in 70% of all tested primary breast cancers. Although this cancer antigen is still in preclinical testing, its strong and restricted pattern of expression in breast cancer makes it a promising target for clinical development. For all cancer vaccines there is mounting evidence that the stage of disease to be targeted is minimal residual disease or in adjuvant settings.