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

Jin Zheng*, Weiqing Jing, Rimas J. Orentas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 λ 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.

Original languageEnglish (US)
Pages (from-to)980-990
Number of pages11
JournalActa biochimica et biophysica Sinica
Volume41
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Costimulatory molecule
  • Neuroblastoma
  • SEREX
  • Treg blockade

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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