Run Polio, Run! Immune System: 3, Cancer: 1

Polio, has taken a toll on thousands of people in the early sixties; however, for the most part, has been eradicated;.  

Years later, who knew that Polio's legacy would not end there. In fact, may very well be the conduit for the cure of Cancer.

For about a century, we’ve been toying with the idea that viruses can be used constructively to trigger our own immune system to attack cancer cells; however only recently have our technological advances in genetic engineering allowed such a tactic to succeed.  Enter Polio as the delivery system.

At Duke Brain Tumor Center it was derived that this particular virus, if entered in the tumor – triggered a tremendous immune response in the body that actually eradicated the cancer cells.  To date, three patients have been in remission that should have been dead in less than a year, but in one case, three years have passed and he is cancer free.  This particular treatment is still in trial phase; however, later this year, the FDA may grant “Breakthrough” status allowing this treatment to be available to many other patients nationwide.  Now this treatment did have its setbacks, for in early trials they gave a patient 3 times the amount of the polio virus to see if the response was better with higher doses, it wasn’t, the patient’s immune response was too great and the patient opted to discontinue treatment and summarily expired because of it.  However, armed with this, doctors used only 15% of the amount previously successful patients have had and using immune suppressants reaped very positive results.  Subsequently zeroed in on the amount of polio virus that could be used safely.

A Brief Background About 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.  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.

What is the Clinical Experience with PVS-RIPO? 

The FDA approved clinical trials with PVS-RIPO in brain tumor patients recently. Since May 2012, five brain tumor patients have been treated. Remarkably, there have been no toxic side effects with PVS-RIPO whatsoever, even at the highest possible dose (10 billion infectious virus particles).

There have been very encouraging signs in patients treated with PVS-RIPO. The first patient enrolled in our study (treated in May 2012) had her symptoms improve rapidly upon virus infusion (she is now symptom-free), had a response in MRI scans, is in excellent health, and continues in school 9 months after the return of her brain tumor was diagnosed. Four patients enrolled in our trial remain alive, and we have observed similarly encouraging responses in other patients. One patient died six months following PVS-RIPO infusion, due to tumor regrowth.

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:

• against glioblastoma brain tumors in adults. We are planning Phase II/III trials in patients with glioblastoma; 

• 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;

• 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 

• explain why/how PVS-RIPO kills cancer cells selectively; 

• unravel how the patients’ immune system responds to tumor infection with PVS-RIPO; and 

• how this immune response fights the tumor itself.

A Statement on Eligibility for Enrollment in the PVS-RIPO Trial. 

The PVS-RIPO trial is available for recurrent glioblastoma patients with only one tumor. The tumor must be surgically accessible; the size must be no smaller than 1 cm and no larger than 5 cm, and the tumor must be located at least 1 cm away from the ventricles. Prior exposure to bevacizumab (Avastin) is permitted. For further information please contact the Preston Robert Tisch, Brain Tumor Center at Duke at (919) 684-5301.

Source:

• http://www.cancer.duke.edu/btc/modules/Research3/index.php?id=41

So “Once more unto the breach, dear friends, once more;”

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About Rick Ricker

An IT professional with over 22 years experience in Information Security, wireless broadband, network and Infrastructure design, development, and support.

For more information, contact Rick at (800) 399-6085 x502