Development of vaccines against self-antigens: the p53 paradigm.
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.
Chada
Sunil
S
Introgen Therapeutics Inc, 2250 Holcombe Boulevard, Houston, TX 77030, USA. s.chada@introgen.com
Mhashilkar
Abner
A
Roth
Jack A
JA
Gabrilovich
Dmitry
D
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000628:therapy*; D015513:Oncogene Proteins / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53