Just last week (April 6, 2010), scientists at the Rush University Medical Center in Chicago completed the second phase of trials for a very promising melanoma vaccine. The trial, which had stunning results, was conducted on 50 patients with metastatic melanoma, which is melanoma that had spread to multiple parts of the body. Currently treatments for advanced melanoma include chemotherapy and immunological drugs which are only effective 15 % of the time. This new vaccine is not only easy to administer, but it also appears to have a much higher response rate in patients, potentially making it the best treatment option for anyone with advanced melanoma.
Melanoma is a rare but deadly cancer that typically begins in a mole or other pigmented tissue and can easily be removed if caught early. If it advances it is much harder to treat and without treatment the patient usually has only a few years to live.
The vaccine being tested in this study is known as OncoVEX. OncoVEX is effective because it is composed of an oncolytic virus, or a reprogrammed virus that is made to attack cancerous cells while leaving healthy cells undamaged. The vaccine is injected directly into lesions that can be felt or seen, and its ease of administration allows it to be given right in a physician’s office.
According to Dr. Howard Kaufman, the director of the Rush Cancer Program, “The vaccine worked not just on the cells we injected, but on lesions in other parts of the body that we couldn’t reach.” He explains how these injections prompt an immune response that circulates through the bloodstream to other affected parts of the body.
In the second phase of trials for OncoVEX, 50 patients were given up to 24 injections of the vaccine over the course of several months, leading to 4 partial and 8 full recoveries. The scientists found these results very promising and Kaufman stated that, “These are the best results to date for any vaccine developed for melanoma, but they need to be confirmed in a larger population.”
To confirm these results, Kaufman is set to lead a third phase of trials which will enroll approximately 430 patients from cancer centers across the U.S. These patients will be tracked for two years after their first dose and if the results are anything like the previous trial, this vaccine could turn an advanced melanoma diagnosis from a death notice into a treatable disease.
The ability of a common virus known as CMV to cause a “superinfection” and infect humans multiple times has puzzled scientists until recently. Researchers at the Oregon Health and Science University Vaccine and Gene Therapy Institute have reported the mechanism that CMV uses to evade the immune system and re-infect humans, in a study published in the April 2nd issue of Science. Their findings shed light on how this virus may be used in the development of CMV-based vaccines for other diseases.
Cytomegalovirus (CMV) does something that not many viruses can do: it can re-infect people who previously have been infected by CMV and have already developed an immune response to the virus. This is unusual for a virus, because the immune system usually “remembers” previous infections with viruses and other pathogens and can mount a strong immune response upon re-infection with a specific pathogen.
The researchers studied CMV-infected monkeys in order to understand how the virus overcomes detection by the immune system. They discovered that CMV avoids a special type of white blood cell called CD8+ T cells, which are responsible for killing cells that are infected with a pathogen. CD8+ T cells recognize infected cells by small molecules on the exterior surface of infected cells known as MHC I. These molecules display small pieces of an invading pathogen and present them to the T cells. This presentation of infectious material ultimately signals T cells to start destroying infected cells.
In order to evade these T cells, CMV makes proteins that interferes with the presentation of viral pieces by MHC I molecules and stops them from recruiting T cells to infected cells. “In essence, CMV is able to cut off an infected cell’s call for elimination. This allows CMV to overcome this critical immune barrier during re-infection,” explains author Klaus Frueh.
The study has interesting implications in the design of CMV-based viral vaccine vectors. Viral vaccine vectors contain a modified, harmless virus that carries a vaccine for another pathogen to the body. Although the body develops immunity to the pathogen, it also develops immunity to the viral vector, which means that the viral vector can only be used for one type of vaccine. Since CMV does not elicit an immune response upon re-infection, it makes an attractive vaccine vector candidate that could potentially carry vaccines against other pathogens, such as HIV, hepatitis C, tuberculosis, and malaria.
CMV is a member of the herpesvirus family and infects 50-80% of the US population by age 40. Most people do not have any symptoms of CMV infection and do not become ill. But for those with weakened immune systems, including infants and the immunocompromised, CMV can cause serious complications. With this new understanding of how CMV evades the immune system, scientists may be able to start utilizing the virus for the benefit of human health.
An obscure virus that does not harm human cells has been generating a wave of excitement in the scientific community. So what is the big deal? A team of researchers from UCLA has reported the 3D structure of the vesicular stomatitis virus (VSV) in a break-through study published in the February 5th edition of Science (full article). Their findings may shed light on how VSV can be manipulated and used in the treatment of cancer and in the development of vaccines for HIV and other harmful viruses.
The researchers used advanced, cutting-edge imaging techniques to visualize the 3D structure of VSV, which appears to have a bullet shaped head and cylindrical trunk. They also characterized how the virus comes to form this bullet shape. With this additional level of understanding of the physical structure of the virus, scientists believe that they can find ways to modify the structure of the virus and use it to treat and prevent illnesses such as cancer and AIDS.
As author Z. Hong Zhou remarked, “This work moves our understanding of the biology of this large and medically important class of viruses ahead in a dramatic way.”
VSV is a model virus that scientists use in the laboratory to study dangerous viruses that cause illnesses such as the flu, measles, and rabies. Previous studies have shown that VSV can detect and kill human cancer cells. Other studies have addressed the question of how to manipulate the virus to deliver a vaccine against HIV to the human body.
(Video is a 3D animation of the lower trunk structure of VSV-source)
A closer look at vaccine technology
A current trend in vaccine development is to use harmless viruses as “vectors” that can carry a specific vaccine to human cells. These viruses have been engineered in the laboratory to carry pieces of genetic material from other pathogens and when they attach to human cells, they inject this genetic material into the cells. These actions mirror an infection by the pathogen itself, although the virus vector does not actually cause an infection, and stimulates an immune response. The human body then remembers how to respond to this pathogen the next time it encounters the pathogen and the body is protected from infection.
Modified versions of the viruses that cause the common cold and small pox are being studied in addition to VSV for use as vaccine vectors. Given the potential that this type of vaccination has to prevent deadly infections from viruses and bacteria, this is an area of research one should surely keep an eye on.