YB-1 immunization combined with regulatory T-cell depletion induces specific T-cell responses that protect against neuroblastoma in the early stage

Authors: Zheng, Jin; Liu, Ping; Yang, Xiaofeng

Source: Acta Biochimica et Biophysica Sinica, 25 December 2012, vol. 44, no. 12, pp. 1006-1014(9)

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Abstract:

Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Currently, no effective clinical treatments are available for advanced neuroblastoma. In a previous study, we screened Y Box protein 1 (YB-1) as a potential neuroblastoma-associated antigen from sera of AGN2a-immunized mice by serological analysis of recombinant cDNA expression libraries technique. The aim of this study is to explore if YB-1 immunization in the context of Treg depletion could induce protective immune response against the neuroblastoma in mice. YB-1 was expressed and purified by pET-15b prokaryotic expression system. It was demonstrated that anti-YB-1 CD8+ T-cell responses could be induced by AGN2a immunization, and the strongest CD8+ T-cell responses against AGN2a were induced by YB-1-immunized mice in the context of Treg depletion compared with YB-1 only immunization group and control group. Importantly, the survival rate of mice treated with YB-1 immunization combined with Treg depletion was 80% when challenged by 1 × 104 AGN2a cells, significantly higher than that of mice immunized with YB-1 alone (P < 0.01). Furthermore, T-cell adoptive therapy showed that the neuroblastoma growth was inhibited when T cells or splenic cells from YB-1-immunized mice with Treg depletion were transferred to AGN2a bearing mice. Both CD4+ and CD8+ T cells were involved in the anti-neuroblastoma responses induced by YB-1 immunization combined with Treg depletion. These results indicated that YB-1 immunization combined with Treg depletion could induce specific T-cell responses against neuroblastoma and could be a potential strategy for the prevention and treatment of neuroblastoma in the early stage.

Keywords: CD25; YB-1; immunization; neuroblastoma

Document Type: Research Article

DOI: http://dx.doi.org/10.1093/abbs/gms089

Publication date: December 25, 2012

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