p53-based immunotherapy of cancer. Approaches ro reversing unresponsiveness to T lymphocytes and preventing tumor escape.

Genetic alterations in p53 are common to a wide range of human tumors, including squamous cell carcinomas of the head and neck. Given the need for novel adjuvant therapies for this disease and the renewed interest in immunotherapy as an adjuvant therapy, p53 has become an attractive candidate for vaccines to treat patients. Although p53 is frequently mutated, the remainder of the molecule keeps its wild-type sequence (wt). As a consequence, several nonmutated peptides can be processed from the altered p53 molecules and presented by tumor cells for T cell recognition. Thus, the targeting of wt p53 peptides represents an approach to developing broadly applicable cancer vaccines. Like most things, however, targeting p53 seems more difficult than originally thought. Whether these difficulties can be circumvented remains to be determined. The development of p53-based vaccines over the past decade is reviewed together with the promising initial findings of their clinical introduction.