Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.
Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.
复制标题
使用 surgifoam 配制二价前列腺癌疫苗可在 PSA 转基因小鼠中引发抗原特异性效应 T 细胞。
DOI：
10.1016/j.vaccine.2017.09.037
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发表时间：
2017
期刊：
影响因子：
5.5
通讯作者：
Karan,Dev
中科院分区：
文献类型：
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作者：
Karan,Dev
我们先前开发并表征了一种基于腺病毒的前列腺癌疫苗，用于同时靶向前列腺特异性抗原（PSA）和前列腺干细胞抗原（PSCA）。我们还证明了用二价疫苗（Ad 5-PSA+PSCA）免疫小鼠抑制了已建立的前列腺肿瘤的生长。然而，有多种挑战阻碍了免疫疗法在临床上的成功。主要关注的问题之一是克服长期效应T细胞的免疫耐受性和维持。在本研究中，我们进一步表征了二价疫苗（Ad 5-PSA+PSCA）在小鼠前列腺中表达人PSA的转基因小鼠模型中的使用。我们证明了PSA的表达分析在mRNA水平（通过RT-PCR）和蛋白质水平（通过免疫组织化学）在前列腺叶收获从PSA转基因（PSA-Tg）小鼠。我们确定，如通过IFN-γ分泌和体外细胞毒性T细胞测定所测量的，向PSA-Tg小鼠施用在Surgifoam中的二价疫苗诱导强PSA特异性效应CD 8 +T细胞。此外，使用Surgifoam与Ad 5-PSA+PSCA疫苗允许多次加强接种，抗原特异性CD 8 +T细胞显著增加。这些观察结果表明，二价前列腺癌疫苗（Ad 5-PSA+PSCA）与Surgifoam的制剂绕过了中和抗体应答，从而允许多次加强。该制剂还有助于在自身抗原存在下诱导抗原特异性免疫应答，并维持长期效应CD 8 +T细胞。
We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad5-PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad5-PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8+T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad5-PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8+T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad5-PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8+T cells.