Researchers from the Duke Cancer Institute have exploited the affinity of Polio virus towards the nerve cells to target the brain tumours, either primary or metastatic.
Professor Matthias Gromeier, microbiologist at Duke University in North Carolina, crippled the lethality potential of polio virus, while preserving the infectivity potential by changing its genetic component called “IRES” ( Internal ribosomal entry site) with that of common cold virus (Rninovirus).
IRES enables a virus to express its own genetic information inside the host cell, it has invaded. They prepared a therapy, known as PVSRIPO, when injected to the brain tumour (Glioblastoma), destroyed it within a short time, in animal models.
When mice and monkeys with malignant glioma were injected with the hybrid polio virus therapy, they recovered completely after just one dose.
Of seven patients involved in the preliminary study, three have responded well to the therapy. One year after treatment, one of the three patients remains cancer-free. Another is disease-free after 11 months; a third has been cancer-free for five months. Two others are also disease-free. Only two patients in the study did not respond well to the therapy.
In contrast, the researchers noted that about 50 percent of glioblastoma patients have a recurrence of their disease within eight weeks of traditional treatment.
They have selected the genetic element of rhinovirus to substitute that of polio virus because it typically does not infect the nerve cells.
Normal brain cells lack the appropriate environment required for the rhinovirus IRES to begin translating the polio virus's genetic information.
Contrary to the normal cells, Cancer cells, regulate gene expression very differently. They grow faster, lack growth inhibitors and generally provide a supportive environment that is highly susceptible to viruses of all sorts, making viruses an excellent invader to disrupt cancer's growth.
Brain tumours express abnormally high number of CD155 receptors and polio infects brain cells by binding to those "docking site" outside of motor neurons. Though the modified polio virus still enters normal motor neurons because it shares the same CD155 receptor as brain tumour cells, but it can no longer grow in normal cells.
The advantage of virus therapy is that it don't carry the toxic side effects of chemotherapy and radiation.
It is difficult to treat brain tumours by chemotherapy because most of chemotherapeutic agents do not cross the blood brain barrier; and targeting the tumours interspersed with normal cells with radiation is also difficult.
This therapy has advantages because the modified polio virus is directly injected into the brain tumour. Once there, the virus seeks out and destroys cancerous cells without being detected by the body's immune system.
The immune system would normally neutralize the polio virus in vaccinated individuals because they have built up antibodies against polio. But the brain does not have immunity against polio because antibodies do not cross the blood-brain barrier. Hence, infusing the brain directly with modified polio is the most effective method of killing cancer cells.
To explain the molecular mechanism that causes the rhinovirus IRES to function in cancer cells, but to malfunction in normal neurons, the researchers discovered that the IRES from the rhinovirus communicates with the opposite end of the polio virus genome, called the 3 prime non-translated region via a set of proteins, called co-factors; which ignite the IRES to begin functioning.
Normal motor neurons, however, may not provide the appropriate set of co-factors to stimulate rhinovirus IRES function. Hence, the modified virus cannot grow in normal motor neurons.
More research may be required to finally recommend the therapy to the deserving patients.
Professor Matthias Gromeier, microbiologist at Duke University in North Carolina, crippled the lethality potential of polio virus, while preserving the infectivity potential by changing its genetic component called “IRES” ( Internal ribosomal entry site) with that of common cold virus (Rninovirus).
IRES enables a virus to express its own genetic information inside the host cell, it has invaded. They prepared a therapy, known as PVSRIPO, when injected to the brain tumour (Glioblastoma), destroyed it within a short time, in animal models.
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| English: Electron micrograph of the poliovirus. Poliovirus is a species of Enterovirus, which is a Genus in the family of Picornaviridae, and is an RNA virus. Deutsch: Polioviren im Transmissionselektronenmikroskop. Français : Le virus de la polio. 日本語: ポリオウイルス. Türkçe: Polio virüsü. తెలుగు: ట్రాన్స్మిషన్ ఎలక్ట్రాన్ మైక్రోస్కోప్లో కనిపించే పోలియో వైరస్. Basa Sunda: Virus polio. (Photo credit: Wikipedia) |
When mice and monkeys with malignant glioma were injected with the hybrid polio virus therapy, they recovered completely after just one dose.
Of seven patients involved in the preliminary study, three have responded well to the therapy. One year after treatment, one of the three patients remains cancer-free. Another is disease-free after 11 months; a third has been cancer-free for five months. Two others are also disease-free. Only two patients in the study did not respond well to the therapy.
In contrast, the researchers noted that about 50 percent of glioblastoma patients have a recurrence of their disease within eight weeks of traditional treatment.
They have selected the genetic element of rhinovirus to substitute that of polio virus because it typically does not infect the nerve cells.
Normal brain cells lack the appropriate environment required for the rhinovirus IRES to begin translating the polio virus's genetic information.
Contrary to the normal cells, Cancer cells, regulate gene expression very differently. They grow faster, lack growth inhibitors and generally provide a supportive environment that is highly susceptible to viruses of all sorts, making viruses an excellent invader to disrupt cancer's growth.
Brain tumours express abnormally high number of CD155 receptors and polio infects brain cells by binding to those "docking site" outside of motor neurons. Though the modified polio virus still enters normal motor neurons because it shares the same CD155 receptor as brain tumour cells, but it can no longer grow in normal cells.
The advantage of virus therapy is that it don't carry the toxic side effects of chemotherapy and radiation.
It is difficult to treat brain tumours by chemotherapy because most of chemotherapeutic agents do not cross the blood brain barrier; and targeting the tumours interspersed with normal cells with radiation is also difficult.
This therapy has advantages because the modified polio virus is directly injected into the brain tumour. Once there, the virus seeks out and destroys cancerous cells without being detected by the body's immune system.
The immune system would normally neutralize the polio virus in vaccinated individuals because they have built up antibodies against polio. But the brain does not have immunity against polio because antibodies do not cross the blood-brain barrier. Hence, infusing the brain directly with modified polio is the most effective method of killing cancer cells.
To explain the molecular mechanism that causes the rhinovirus IRES to function in cancer cells, but to malfunction in normal neurons, the researchers discovered that the IRES from the rhinovirus communicates with the opposite end of the polio virus genome, called the 3 prime non-translated region via a set of proteins, called co-factors; which ignite the IRES to begin functioning.
Normal motor neurons, however, may not provide the appropriate set of co-factors to stimulate rhinovirus IRES function. Hence, the modified virus cannot grow in normal motor neurons.
More research may be required to finally recommend the therapy to the deserving patients.
