Abstract
BackgroundWe have developed a cell-based vaccine that features the expression of both CD80 and CD86 on the surface of a murine neuroblastoma cell line. The cellular immunity induced by this vaccine is enhanced by treatment with antibody that interferes with T-regulatory cell (Treg) function and we report here that immunization combined with interfering with Treg function also produces a profound serological effect. Serum from mice immunized with our cell-based vaccine in the context of Treg blockade was used to screen a cDNA expression library constructed from the parental neuroblastoma tumor cell line, AGN2a.ResultsSerum from mice vaccinated in the context of Treg blockade identified a number of potentially oncogenic transcripts that may serve as important immune targets in a tumor-derived cDNA library screen. This novel approach identified far more candidates than could be seen with serum derived from vaccine-treated only, Treg-depleted only, or tumor-bearing mice. The most commonly identified tumor-associated antigen, using serum from immunized and Treg-depleted mice, was the DEK oncogene. Altered expression of the DEK oncogene has been implicated in a number of human cancers. Importantly, we were able to demonstrate that the DEK oncogene also induces a T cell response.ConclusionThe use of post-vaccine immune serum in this report differs from previous approaches where serum collected at the time of cancer onset or diagnosis and was used for tumor antigen identification. We hypothesize that the use of diagnostic serum samples may be inadequate for the clinical translation of this approach, and that identification of protective immunogenic tumor antigens may require the use of serum from post-treatment or vaccinated subjects. The identification of DEK as a tumor-associated antigen 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.
Highlights
We have developed a cell-based vaccine that features the expression of both CD80 and CD86 on the surface of a murine neuroblastoma cell line
We constructed a cDNA library using mRNA purified from the AGN2a cell line and expressed proteins encoded by tumor- derived mRNA in E. coli using the λZAPII phage system
Fiftyeight unique plaques were identified as expressing proteins that could be recognized by IgG antibody when serum from AGN2a-CD80/CD86+PC61 treated mice was used at a dilution of 1:250
Summary
We have developed a cell-based vaccine that features the expression of both CD80 and CD86 on the surface of a murine neuroblastoma cell line. Our own work has demonstrated that cancer cell-based vaccines expressing multiple immune co-stimulatory molecules in the murine neuroblastoma cell line AGN2a can transform this tumor cell line in to a vaccine that induces strong cell-based immunity to the unmodified parental cell line [8,9]. Based on the ability to induce an immune response with cancer cell-based vaccines, human trials with neuroblastoma patients have been carried out [10]. These cell-based cancer vaccines did not prove immediately effective, they were demonstrated to be safe and are ripe for further optimization [11]
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