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Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 702146, 11 pages
http://dx.doi.org/10.1155/2011/702146
Review Article

Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

1Department of Gynecologic Oncology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
2Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
3Departments of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
4Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

Received 23 September 2010; Revised 13 December 2010; Accepted 18 January 2011

Academic Editor: Peter Bretscher

Copyright © 2011 R. Vermeij et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients.