Overcoming the hurdles of randomised clinical trials of therapeutic cancer vaccines.

Most of the recent randomised clinical trials of therapeutic cancer vaccines have failed to demonstrate a meaningful therapeutic benefit to patients over existing treatments. Furthermore, some clinical trials have demonstrated a detrimental effect on patients, resulting in poorer outcomes. These unexpected results have shed light on several important issues to be solved for further development of cancer vaccines. As has been discussed with respect to the use of granulocyte-macrophage colony-stimulating factor (GM-SCF) as an adjuvant, the failures of clinical trials may be explained, in part, by a vaccine-specific adverse event, i.e. the induction of an 'inconvenient immune response' that inhibits pre-existing host immunity. This hypothesis may be supported by the fact that randomised trials of personalised peptide vaccines that were selected in consideration of pre-existing host immunities in individual patients resulted in clear benefit to patients. The development of reliable biomarkers for the selection of appropriate patients and vaccine antigens would thus be pivotal to prevent such vaccine-specific adverse events. This article discusses possible ways to overcome the hurdles of randomised clinical trials of therapeutic cancer vaccines based on a review of recently conducted clinical trials. Copyright 2010 Elsevier Ltd. All rights reserved.