Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Gene Ther. 2010 Jun;17(6):805-10. doi: 10.1038/gt.2010.20. Epub 2010 Mar 11.
Prostate cancer is one of the most prevalent cancers in men. Replication-competent oncolytic herpes simplex virus (oHSV) vectors are a powerful antitumor therapy that can exert at least two effects: direct cytocidal activity that selectively kills cancer cells and induction of antitumor immunity. In addition, oHSV vectors can also function as a platform to deliver transgenes of interest. In these studies, we have examined the expression of a xenogeneic homologue of the prostate cancer antigen, prostatic acid phosphatase (PAP), with the goal of enhancing virotherapy against PAP-expressing tumors. PAP has already been used for cancer vaccination in patients with prostate cancer. Here we show that treatment with oHSV bPDelta6 expressing xenogeneic human PAP (hPAP) significantly reduces tumor growth and increases survival of C57/BL6 mice bearing mouse TRAMP-C2 prostate tumors, whereas expression of syngeneic mouse PAP (mPAP) from the same oHSV vector did not enhance antitumor activity. Treatment of mice bearing metastatic TRAMP-C2 lung tumors with oHSV-expressing hPAP resulted in fewer tumor nodules. To our knowledge, this is the first report of oncolytic viruses being used to express xenoantigens. These data lend support to the concept of combining oncolytic and immunogenic therapies as a way to improve therapy of metastatic prostate cancer.
前列腺癌是男性中最常见的癌症之一。复制型溶瘤单纯疱疹病毒（oHSV）载体是一种强大的抗肿瘤治疗方法，可发挥至少两种作用：直接细胞毒性活性，选择性杀死癌细胞和诱导抗肿瘤免疫。此外，oHSV 载体还可以作为递送感兴趣的转基因的平台。在这些研究中，我们研究了前列腺癌抗原前列腺酸性磷酸酶（PAP）的异种同源物的表达，目的是增强针对表达 PAP 的肿瘤的病毒疗法。PAP 已用于前列腺癌患者的癌症疫苗接种。在这里，我们表明，用表达异种人 PAP（hPAP）的 oHSV bPDelta6 治疗可显著减少 C57/BL6 小鼠携带的小鼠 TRAMP-C2 前列腺肿瘤的生长并提高其存活率，而来自同一 oHSV 载体的同种小鼠 PAP（mPAP）的表达并没有增强抗肿瘤活性。用表达 hPAP 的 oHSV 治疗携带转移性 TRAMP-C2 肺肿瘤的小鼠可导致肿瘤结节减少。据我们所知，这是首次报道使用溶瘤病毒表达异种抗原。这些数据支持将溶瘤和免疫治疗相结合作为改善转移性前列腺癌治疗的概念。
