Development of vaccines against self-antigens: the p53 paradigm

Curr Opin Drug Discov Devel. 2003 Mar;6(2):169-73.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / therapeutic use*
  • Clinical Trials as Topic
  • Dendritic Cells / immunology
  • Genes, Tumor Suppressor
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy, Adoptive
  • Neoplasms / therapy*
  • Oncogene Proteins / immunology
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Oncogene Proteins
  • Tumor Suppressor Protein p53