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Gene-based vaccine strategies against cancer

机译：基于基因的抗癌疫苗策略

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In recent years, the characterization of gene-based cancer vaccines has been an important step in the development of different treatment options for human carcinoma. These particular vaccines make use of proteins that are specifically produced at very high levels by tumor cells. These tumor-associated antigens (TAAs) are not only used in diagnostic situations, but also in the development of cancer vaccines. In this review we will focus on two well characterized TAAs, carcinoembryonic antigen (CEA) and prostate specific antigen (PSA). The two methods of in vivo delivery we will examine are recombinant vaccinia virus and nucleic acid immunization. The TAA gene can be cloned into vaccinia virus and the viral infection stimulates an adequate immune response in the host. In the case of nucleic acid immunization, DNA constructs encoding for TAAs are directly injected into the host and are taken up by its cells. The cells express the specific encoded antigen upon which the immune system acts.The effects of CEA recombinant vaccinia virus (rV-CEA) have been characterized in rodents, macaques, and humans. It was shown that the vaccine induced both humoral and cellular immune responses in mice and monkey models. In a phase I clinical trial, a CEA-specific cytotoxic T- lymphocyte response was observed. The effects of a CEA DNA vaccine were investigated in both mice and dogs and both humoral and cellular immune responses were found as well. A recombinant vaccinia virus expressing PSA was tested in rhesus monkeys and induced a PSA-specific long term cellular immune response. Experiments were also performed injecting a PSA DNA construct into both mice and rhesus monkeys. PSA-specific humoral and cellular immune responses were observed in both cases. All these experimental approaches demonstrate the efficacy and advantages of gene- based cancer vaccine strategies and support further clinical investigations.
机译：近年来，基于基因的癌症疫苗的表征已成为开发针对人类癌症的不同治疗方案的重要一步。这些特定的疫苗利用了由肿瘤细胞高水平特异性产生的蛋白质。这些肿瘤相关抗原（TAA）不仅用于诊断情况，而且还用于开发癌症疫苗。在本文中，我们将重点介绍两种特征明确的TAA，即癌胚抗原（CEA）和前列腺特异性抗原（PSA）。我们将研究的两种体内递送方法是重组牛痘病毒和核酸免疫。可以将TAA基因克隆到牛痘病毒中，病毒感染可以刺激宿主产生足够的免疫反应。在核酸免疫的情况下，将编码TAA的DNA构建体直接注入宿主并被其细胞吸收。细胞表达免疫系统作用的特定编码抗原。CEA重组牛痘病毒（rV-CEA）的作用已在啮齿动物，猕猴和人类中得到了表征。结果表明，该疫苗可在小鼠和猴子模型中诱导体液和细胞免疫反应。在I期临床试验中，观察到CEA特异性细胞毒性T淋巴细胞反应。研究了CEA DNA疫苗在小鼠和狗中的作用，还发现了体液和细胞免疫反应。在恒河猴中测试了表达PSA的重组牛痘病毒，并诱导了PSA特异性的长期细胞免疫应答。还进行了将PSA DNA构建体注射入小鼠和恒河猴的实验。在两种情况下均观察到PSA特异性的体液和细胞免疫反应。所有这些实验方法证明了基于基因的癌症疫苗策略的有效性和优势，并支持进一步的临床研究。

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