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Acta Biochimica et Biophysica Sinica Advance Access published online on November 12, 2009
Acta Biochimica et Biophysica Sinica, doi:10.1093/abbs/gmp092
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Discovery of YB-1 as a new immunological target in neuroblastoma by vaccination in the context of regulatory T cell blockade

Jin Zheng1,*, Weiqing Jing2 and Rimas J. Orentas2

1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, China
2 Department of Pediatrics, Medical College of Wisconsin and the Children's Research Institute, Children's Hospital of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA

* Correspondence address. Tel: +86-29-82655429-812; Fax: +86-29-82655499; E-mail: jzheng{at}mail.xjtu.edu.cn


  Abstract

Neuroblastoma is one of the most common solid tumors in infancy and early childhood. Using the A/J mouse and a syngeneic neuroblastoma cell line AGN2a, we induced a strong anti-neuroblastoma cellular immune response when AGN2a transfected to express costimulatory molecules (CD80/CD86/CD54/CD137L) was used as a vaccine in the context of regulatory T cell blockade. Strong humoral immunity was induced by AGN2a-4p immunization in the context with regulatory T cell blockade. Serum from treated mice was used to screen an AGN2a cDNA expression library that was constructed with {lambda} ZAP express vector in order to identify tumor-associated antigens by SEREX. Twenty-one clones were identified by sequencing and comparative analysis of gene pools. Most transcripts play some roles in the neuronal differentiation, cell metabolism, or have previously been identified as transcripts that are over-expressed in other malignancies. The most commonly identified tumor-associated antigen, using serum from AGN2a-4p immunization with Treg blockade mice, was YB-1 protein that also induced a T cell response. These results indicated that potential neuroblastoma-associated antigens were found by the sera from mice immunized with tumor cells expressing costimulatory molecules with regulatory T cell function blockade. The identification of YB-1 as tumor-associated antigens capable of eliciting a T cell response validates our experimental approach and argues for the antigens we have identified here to be evaluated as targets of effector immunity and as vaccine candidates.

Keywords    neuroblastoma; costimulatory molecule; Treg blockade; SEREX

Received: June 20, 2009; Accepted: October 9, 2009
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