Oncoantigens as anti-tumor vaccination targets: the chance of a lucky strike?
Neoplastic transformation is a multistage process and distinct gene products of specific cell regulatory pathways are involved at each stage. Identification of genes overexpressed at a specific stage provides an unprecedented opportunity to address the immune system against antigens with a driving role in tumor progression (oncoantigens). The ERBB2 oncogene is a prototype of deregulated oncogenic protein kinase membrane receptors. Mice transgenic for rat ERBB2 (BALB-neuT mice) were used in this study to identify an additional set of oncoantigens expressed at defined stages by most breast carcinomas to be used as alternatives to ERBB2-driven vaccination. To address this question, we integrated the transcription data generated by comparing preneoplastic lesions and neoplasia in BALB-neuT mice with a meta-analysis on transcription profiles generated from normal and breast tumor human specimens. Forty-six putative oncoantigens identified and prioritized according to their expression on the cell membrane or in the extra cellular space, cytoplasm and nucleus were chosen for preclinical investigation as vaccination targets.
Calogero
Raffaele Adolfo
RA
Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin, Italy.
Quaglino
Elena
E
Saviozzi
Silvia
S
Forni
Guido
G
Cavallo
Federica
F
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases