Mol Ther. :科学家开发出口服乳腺癌疫苗

美国辛辛那提大学(UC)癌症研究所和美国国家健康中心（NIH）科学家开发出一种新型口服疫苗，该疫苗能够刺激免疫系统防止乳腺癌发生。科学家首次利用了AAV病毒来研制的口服癌症疫苗。相关报道发表在一月份的Molecular Therapy上。

尽管其他口服乳腺癌疫苗已经在模式动物上进行了实验，但是由于其基于细菌研制对人体安全有潜在隐患，所以这些疫苗的安全性还有待验证。

UC科学家和NIH科学家一起试图用AAV病毒来开发一类疫苗。因为该病毒对人体几乎没有任何副作用，并且现阶段已经用来作为基因疗法治疗家族型遗传病。

Steel博士指出AAV病毒的特异之处在于它们在胃中依然有活性。正常情况下，当病毒由口引入胃中后，往往病毒会被降解。而AAV病毒却不能被降解，这就为研制口服癌症疫苗提供了有利条件。

在本次临床前动物实验中，研究人员检测了两种AAV病毒，一种能够穿过胃壁进入血液中，另一种不能。研究结果显示这两种病毒在短期和长期减少乳腺癌发病方面有作用。研究人员也采用了更有效的方法--口服加肌肉注射。

Steel称不能穿过胃壁的AAV病毒比能够穿过胃壁的在预防乳腺癌上效果更好--治疗的一年后100%的实验动物没有产生乳腺癌。而且口服比肌肉注射更有效。

研究人员称基于AAV病毒的口服癌症疫苗是已经被诊断为某种类型乳腺癌或者有高风险的人的保护自己的有力武器。

UC科学家开始开发基于AAV病毒的针对其他诸如肺癌等的其他癌症的口服疫苗。

原文链接：

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Oral Vaccination With Adeno-associated Virus Vectors Expressing the Neu Oncogene Inhibits the Growth of Murine Breast Cancer

Steel JC, Di Pasquale G, Ramlogan CA, Patel V, Chiorini JA, Morris JC.

Recombinant adeno-associated viruses (AAV) have been used for therapeutic gene transfer. These vectors offer a number of advantages including resistance to the effects of pH, a broad cellular tropism, efficient gene transfer, persistence of gene expression, and little toxicity. AAV vectors; however, at high doses can induce humoral and cellular immune responses. While potentially problematic for replacement gene therapy, this effect may be advantageous for antitumor vaccination. We examined the activity of an oral and intramuscular antitumor vaccination using AAV serotypes 5 and 6 expressing a truncated neu oncogene in a neu-positive murine TUBO breast cancer model. Mice receiving a single oral administration of AAV5-neu or AAV6-neu demonstrated improved survival. Oral vaccination significantly improved survivals compared with intramuscular vaccination. Mice vaccinated with AAV6-neu survived longer than those treated with AAV5-neu. Vaccination with AAV5-neu or AAV6-neu induced both humoral and cellular immune responses against the NEU antigen. These responses were more robust in the mice undergoing oral vaccination compared with mice receiving the intramuscular vaccination. Protection from tumor was long lasting with 80% of the animals treated with oral AAV6-neu surviving a re-challenge with TUBO cells at 120 and 320 days post-vaccination. Further evaluation of AAV-based vectors as tumor vaccines is warranted。

来源：生物谷