Humoral immune response induced by an engineered cell-based neuroblastoma vaccine with or without CD25 blockade

Neuroblastoma is the most common extracranial solid cancer in childhood and it can develop in the nerve tissue of the adrenal gland, neck, chest, or spinal cord. A number of tumor-associated antigens (TAAs), which can elicit humoral immunity, have been identified in cancer patients. To investigate the humoral immunity during neuroblastoma development, we treated A/J mice with an aggressive clone of neuroblastoma (AGN2a) cells, then vaccinated the mice with cells expressing AGN2a-CD80/CD137L under the conditions with or without regulatory T cell blockade. Strong humoral immunity was induced by AGN2a-CD80/CD137L immunization in the context of regulatory T cell blockade. Sera from treated mice were used to screen an AGN2a cDNA expression library for identifying TAAs by SEREX (serological analysis of recombinant cDNA expression libraries). Clones were identified by sequencing and comparative analysis of gene pools. Further investigation of these gene products revealed that most of them play a role in the neuronal differentiation, cell metabolism, and are highly expressed in other types of malignancy. Asz1 (ankyrin repeat, SAM, and basic leucine zipper domain-containing protein) was found in all tumor-bearing groups. These results implicated that these candidates identified from tumor-bearing mice may be neuroblastoma-associated antigens, which can be used as biomarkers in early diagnosis of neuroblastoma, whereas those identified from vaccinated mice may be the potential therapeutic targets.