Development of vaccines against self-antigens: the p53 paradigm

Abstract

Active immunotherapy using dendritic cells (DCs) to deliver tumor antigens has generated considerable excitement among oncologists worldwide. Although most tumor antigens used in immunotherapeutic approaches are tumor-associated, often, little is known about the underlying biology of the target. Here, we review the use of 'obligate' tumor antigens, where antigen expression is a prerequisite for tumor formation or maintenance. The prototype for this class of antigens is the p53 tumor antigen, which is mutated in > 50% of human malignancies. The direct involvement of p53 in the malignant transformation of tumors makes it an attractive target for immunotherapy. p53-Reactive antibodies have been found in patients with various types of cancer, demonstrating that the human immune system can recognize and respond to tumor-associated p53. Extensive preclinical experimentation has now validated the translation of p53-expressing DCs into a clinical setting. Clinical trials are ongoing to evaluate the safety and antitumor responses elicited by DCs transduced with adenoviral-p53 in cancer patients.