用病毒治療腦癌 新療法有望獲FDA批准 更新： 2016年05月14日 【記者張秉開／編譯】美國食品及藥品管理局（FDA）證實一項腦癌治療實驗取得突破性進展，臨床醫生可以使用脊髓灰質炎病毒來治療大腦的膠質母細胞瘤（glioblastoma）。 據CBS 5月12日報導，該治療方法的臨床實驗早期療效非常顯著，因此美國食品及藥品管理局希望快速監測全部療效，以便儘早將該治療方法用於臨場應用。CBS在其「60分鐘」（60 Minutes）節目中，對參與該實驗的病人情況進行了兩年的隨訪調查。2011年，一名20歲學生史蒂芬妮．利普斯科姆（Stephanie Lipscomb）因頭痛而被確診患膠質母細胞瘤。當時，史蒂芬妮腦中的腫瘤已經為網球大小，醫生推測她只有幾個月的生命。史蒂芬妮不得不接受手術，切除98%的腫瘤。但在2012年，醫生告訴她癌細胞又回來了。於是，史蒂芬妮成了第一個願意接受新方法治療復發性膠質母細胞瘤的試驗參與者。該新型的療法使用脊髓灰質炎病毒，也就是人們熟知的造成小兒麻痺的病毒。主持新療法的杜克大學分子生物學家馬迪亞斯．格魯梅爾（Matthias Gromeier）解釋，該方法將脊髓灰質炎病毒改變為身體無害的狀態，之後將無害病毒物質導入癌細胞。 而無害的脊髓灰質炎病毒會在癌細胞之中存活，釋放出殺死癌細胞的毒素，而且這個過程也會喚醒身體的免疫功能，去排除癌症細胞。格魯梅爾表示，所有癌症都有保護自己不受免疫功能監控和清除的能力，而新療法就是要打破癌細胞的這種功能。他說：「我們用病毒去感染腫瘤，這樣可以去掉腫瘤的自我保護傘，而讓免疫功能重新發揮作用，處理腫瘤。」 據報導，實驗觀察到脊髓灰質炎病毒確實殺死癌細胞，但是起到主要治療作用的是人體自身免疫功能。史蒂芬妮的腦癌在21個月內不斷縮小，直到消失。2014年8月，核磁共振（MRI）複查史蒂芬妮的情況，沒有發現任何活躍的癌細胞。
A Phase I Clinical Trial for Recurrent Glioblastoma Patients Opens for Accrual at the Preston Robert Tisch Brain Tumor Center Targeting Cancer with Genetically Engineered Poliovirus (PVS-RIPO); PVS-RIPO is a genetically engineered poliovirus that is being investigated as a new anti-cancer agent at the Preston Robert Tisch Brain Tumor Center at Duke. The idea of targeting cancer with viruses has been around for at least 100 years. However, valid strategies of using 'oncolytic' (cancer-fighting) viruses emerged only recently. This is mostly due to technological advances in genetic engineering of viruses. To work against cancers in patients, oncolytic viruses must target cancer cells for infection and they must kill them. At the same time, they must be safe. Accomplishing this is very difficult scientifically and only very few viruses are suitable as cancer-fighting agents in the clinic. We achieved this feat by genetic engineering to remove poliovirus' inherent disease-causing ability (a piece of genetic code of a cold-causing rhinovirus was spliced into the poliovirus genome). PVS-RIPO naturally infects almost all cancer cells, because the receptor for poliovirus (which is used for cell entry) is abnormally present on most tumor cells. PVS-RIPO kills cancer cells, but not normal cells, because its ability to grow (and kill) depends on biochemical abnormalities only present in cancer cells. Safety testing in non-human primates and human patients has shown no nerve cell killing, no ability to cause poliomyelitis, and no ability of PVS-RIPO to change back to wild type poliovirus that can cause poliomyelitis.
MRI of patient on Poliovirus trial How Does PVS-RIPO work? PVS-RIPO is infused directly into a patients' tumor (e.g. in the brain). This assures that the maximal amount of virus is delivered directly to the tumor. Once inside the tumor, PVS-RIPO infects and kills tumor cells. Although this tumor cell killing alone may have tumor-fighting results, the likely key to therapy with PVS-RIPO is its ability to recruit the patients' immune response against the cancer. There are many events following PVS-RIPO infusion into the tumor that can contribute to such an outcome. The human immune system is trained to recognize virus infections and, thus, responds vigorously to the infected tumor. Unraveling why and how the immune system attacks tumors that were infused with PVS-RIPO is a major research goal in the Gromeier Laboratory. What are our Plans for the Future? Currently, Phase I clinical trials of PVS-RIPO against recurrent glioblastoma brain tumors are ongoing at Duke. We plan to extend these studies (Phase II/III) in a quest to establish PVS-RIPO as a possible therapy for brain tumors. In addition, PVS-RIPO has the potential to work for other types of cancers. The reason for this is that the mechanisms responsible for PVS-RIPO's effects against brain tumors broadly apply to almost all cancers.
Clinical Trials. There are several initiatives for further clinical development of PVS-RIPO:
a) against glioblastoma brain tumors in adults. We are planning Phase II/III trials in patients with glioblastoma;
b) against brain tumors in children. The mechanisms that make PVS-RIPO safe and efficacious in adult brain tumors also work for similar types of brain cancers in children. We are planning to investigate PVS-RIPO in children with brain tumors;
c) against tumors other than brain cancers. Because PVS-RIPO naturally targets and destroys cancer cells from most common cancer types (pancreas, prostate, lung, colon, and many others), it can be directed against these cancers as well. To establish this in the clinic, we plan future clinical trials in patients with cancers other than brain tumors. What Do We Need to Make PVS-RIPO a Success Against Cancer? The key to better cancer care is a better understanding of the disease and the mechanisms that may work to fight it. We already have much information about PVS-RIPO, because of a very successful research effort in the Gromeier Laboratory that now spans >10 years. We will continue to identify why anti-tumor responses occur in brain tumor patients infused with PVS-RIPO and how we can best harness them for cancer therapy in general. Research currently ongoing in the Gromeier Laboratory is designed to a) explain why/how PVS-RIPO kills cancer cells selectively; b) unravel how the patients' immune system responds to tumor infection with PVS-RIPO; and c) how this immune response fights the tumor itself.
PVS-RIPO virus The Virus particle consists of a protein shell (blue, red and green shapes) arranged in a symmetric structure. In this image, the particle has been "cracked open," to reveal the virus genome (yellow, pink), which is surrounded by the protein shell. The PVS-RIPO genetic code is based on the Sabin vaccine (yellow) with a piece of genetic information from a common cold virus spliced in (pink).
Source: http://www.cancer.duke.edu/btc/modules/Research3/index.php?id=41
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