Therapeutic vaccination halts disease progression in BALB-neuT mice:: The amplitude of elicited immune response is predictive of vaccine efficacy
Therapeutic vaccination halts disease progression in BALB-neuT mice:: The amplitude of elicited immune response is predictive of vaccine efficacy
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DOI：
10.1089/hum.2007.127
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发表时间：
2008-07-01
影响因子：
4.2
通讯作者：
Scarselli, Elisa
中科院分区：
文献类型：
--
作者：
Cipriani, Barbara;Fridman, Arthur;Scarselli, Elisa
本研究的目的是评估在 BALB-neuT 小鼠乳腺癌模型治疗环境中使用大鼠 ErbB2 抗原进行基因疫苗接种的功效，并建立与疫苗功效的免疫学相关性。为了确定早期治疗环境，我们使用高频超声系统对小鼠乳腺进行了成像研究，从小鼠出生后第 13 周开始，该系统可以在肿瘤病变变得明显之前进行诊断。在此阶段实施了疫苗接种的强化免疫方案，包括每周四次电穿孔DNA注射，然后注射两次腺病毒，该腺病毒携带编码大鼠ErbB2细胞外跨膜结构域的密码子使用优化的cDNA。通过分析外周血白细胞来监测每只小鼠的免疫学参数。接种疫苗的小鼠中第一个可触及肿瘤的出现被延迟，并且在出现额外肿块之前存在统计学上显着的时间间隔，表明疾病稳定。免疫接种的结果是，检测到了针对大鼠 ErbB2 的抗体和 CD8(+) T 细胞，并且引发的反应幅度与疫苗接种的功效相关。此外，疫苗接种方案特别阻止了循环骨髓抑制细胞（MSC）的增加。在疫苗接种结束时测量的所有三个参数，即 CD8(+) T 细胞、大鼠 ErbB2 抗体和循环 MSC，都可以用作未来肿瘤发展的预测生物标志物。这项研究强调了基因疫苗在治疗恶性肿瘤方面的潜力，并建议在临床上进一步验证可能的预测生物标志物，以跟踪接种疫苗的癌症患者。
The aim of this study was to evaluate the efficacy of genetic vaccination with rat ErbB2 antigen in a therapeutic setting for the BALB-neuT mouse model of mammary carcinoma and to establish immunological correlates with vaccine efficacy. To define an early therapeutic setting we performed imaging studies of mouse mammary glands with a high-frequency ultrasound system that allowed the diagnosis of tumor lesions before they become palpable, starting from week 13 after mouse births. An intensive immunization protocol of vaccination was implemented at this stage, consisting of four weekly DNA injections with electroporation followed by two injections of adenovirus carrying the codon usage-optimized cDNA encoding the extracellular-transmembrane domain of rat ErbB2. Immunological parameters were monitored in each individual mouse by analyzing peripheral blood leukocytes. The appearance of the first palpable tumor in vaccinated mice was delayed and there was a statistically significant time gap before additional masses developed, indicating disease stabilization. As a result of the immunization, antibodies and CD8(+) T cells to rat ErbB2 were detected and the amplitude of elicited responses correlated with the efficacy of vaccination. Moreover, the vaccination regimen specifically halted the rise in circulating myeloid suppressor cells (MSCs). All three parameters, that is, CD8(+) T cells, antibodies to rat ErbB2, and circulating MSCs, measured at the end of vaccination could be used as predictive biomarkers for future tumor development. This study emphasizes the potential of genetic vaccines for the therapeutic treatment of malignancies and suggests possible predictive biomarkers to be further validated in the clinic for the follow-up of vaccinated cancer patients.