Tumor antigen analysis in neuroblastoma by serological interrogation of bioinformatic data. Cancer Sci 2010 Nov;101(11):2316-24
Date
08/20/2010Pubmed ID
20718755Pubmed Central ID
PMC3103783DOI
10.1111/j.1349-7006.2010.01694.xScopus ID
2-s2.0-78049437902 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
The identification of tumor antigens remains a major objective in tumor immunology, especially in pediatric malignancies where solid tumors often do not express a single dominant antigen. Methods such as the Serological Screening of Recombinant cDNA Expression Libraries (SEREX) have been used in the discovery of tumor-expressed proteins by virtue of their ability to induce an antibody response. To focus and accelerate this approach, we first identified candidate antigens by gene expression profiling data from clinical neuroblastoma specimens and then used an animal model to generate an antibody response to an engineered cell-based vaccine. Candidate tumor antigens were expressed as recombinant proteins in a mammalian system and screened for antibody recognition using serum from mice vaccinated with a neuroblastoma cell-based vaccine engineered to express CD80 and CD86, with or without Treg depletion. Through this procedure, the never in mitosis A (NIMA)-related kinase NEK2 was identified as a tumor-associated antigen. Direct testing of serum from patients newly diagnosed with neuroblastoma showed specific serological responses in two of 20 patients. Although NEK2 was not universally recognized, it may serve as a tumor antigen for some patients.
Author List
Kohler ME, Johnson BD, Palen K, Chen QR, Khan J, Orentas RJAuthor
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Neoplasm
B7-1 Antigen
B7-2 Antigen
Biomarkers, Tumor
Blotting, Western
Cancer Vaccines
Cell Line, Tumor
Cluster Analysis
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Luciferases
Mice
Mice, Inbred Strains
NIMA-Related Kinases
Neuroblastoma
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Vaccination
