Universal tumor antigens as targets for immunotherapy.
BACKGROUND
Clinically successful Ag-specific cancer immunotherapy depends on the identification of tumor-rejection Ags. Historically, tumor Ags have been identified by analyzing cancer patients' own T-cell or Ab responses.


METHODS
The unveiling of the human genome and optimized immunological analytical tools, particularly 'reverse immunology', have made it possible to screen any given protein for immunogenic epitopes. These advances enable the immunological characterization of universal tumor-associated gene products that mediate critical functions for tumor growth and development.


RESULTS
Four examples of candidate universal tumor Ags reviewed here include the telomerase reverse transcriptase (hTERT), the inhibitor of apoptosis survivin, the p53-interacting protein MDM2, and the cytochrome P450 isoform 1B1--each at various levels of preclinical and clinical development.


CONCLUSIONS
The cardinal feature of universal TAA is that they are expressed in (nearly) all tumors and in no normal tissues. They are directly involved in the malignant phenotype of the tumor. Certain peptides derived from such Ags are expressed on the tumor-cell surface, as evidenced by Ag-specific, MHC-restricted T-cell anti-tumor reactivity in vitro. It is hoped that these features imply a pre-existing, high-affinity T-cell pool that can be activated in vivo in patients, without immunoselection of variant tumor cells no longer expressing the Ag of choice.
Gordan
J D
JD
Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Vonderheide
R H
RH
D000951:Antigens, Neoplasm / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D019295:Computational Biology; D065633:Cytochrome P-450 CYP1B1; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000628:therapy*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019098:Telomerase / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D000939:Epitopes; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000077022:Survivin; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019098:Telomerase