New gene therapy for melanoma A team of researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, in the United States has demonstrated sustained regression of advanced melanoma in a study of 17 patients by genetically engineering patient’s own white blood cells to recognize and attack cancer cells. This is the first time gene therapy has been used successfully to treat cancer. The researchers hope it will be applicable not only to melanoma, but also for a broad range of common cancers, such as breast and lung cancers. Autologous lymphocytes are a person’s own white blood cells that have previously been used to treat metastatic melanoma. In a process called adoptive cell transfer, lymphocytes are first removed from patients with advanced melanoma. Next, the most aggressive tumour-killing cells are isolated, multiplied in the lab, and then reintroduced to patients who have been depleted of all remaining lymphocytes. While reasonably successful, this method can only be used for melanoma patients and only for those who already have a population of specialized lymphocytes that recognize tumours as abnormal cells. NCI researchers, led by Dr. Steven A. Rosenberg, sought an effective way to convert normal lymphocytes in the lab into cancer fighting cells. To do this, they drew a small sample of blood that contained normal lymphocytes from individual patients and infected the cells with a retrovirus in the laboratory. The retrovirus acts like a carrier pigeon to deliver genes that encode specific proteins, called T cell receptors (TCRs), into cells. When the genes are turned on, the TCRs made lodge on the outer surface of the lymphocytes. These TCRs act as homing devices in that they recognize and bind to certain molecules found on the surface of tumour cells. They then activate the lymphocytes to destroy the cancer cells. There were three groups of patients in the study. The first group consisted of three patients who showed no delay in the progression of their disease. As the study progressed, the researchers improved the treatment of lymphocytes in the lab so that the cells could be administered in their most active growth phase. In the remaining two groups, patients received the improved treatments. Two patients experienced cancer regression, had sustained high levels of genetically altered lymphocytes, and remained disease-free over one year. One month after receiving gene therapy, all patients in the last two groups still had 9 per cent to 56 per cent of their TCR-expressing lymphocytes. There were no toxic side effects attributed to the genetically modified cells in any patient. Website: www.chroniclepharmabiz.com

Landmark success for transdermal insulin delivery Phosphagenics Ltd., Australia, announced that it has successfully delivered insulin through the skin using transdermal carrier technology. From one topical application of TPM-02/Insulin as a gel, insulin was shown to safely penetrate the human skin and then be delivered into the blood stream over a sustained period of time. The main objective of the trial was to know the tolerability and safety of TPM-02/Insulin, and this was achieved with no adverse reactions. It also demonstrated the ability of TPM-02/Insulin to deliver insulin into the blood stream at levels high enough to produce significant results. The trials were conducted at the Centre for Clinical Studies in Melbourne, in accordance with ICH GCP standards and under the guidance and supervision of Professor Leon Bach. Blood glucose, insulin levels and the insulin biomarker C peptide were all measured as secondary endpoints. Website: www.biospectrum.com

New findings could lead to vaccine for severe malaria A joint study in Karolinska Institute, Sweden, and Makerere University, Uganda, has produced key findings on how the malaria parasite conceals itself in the placenta, as the most severe form of malaria hits pregnant women and children the hardest. Plasmodium falciparum is the most virulent of the four malaria parasites that infect man. It is particularly dangerous in that it also infects the placenta of pregnant women, with fatal consequences for both her and the foetus. Ms. Niloofar Rasti, a graduate student from Karolinska Institute explained that for some reasons, women in their first pregnancy lose the semi-immunity that is normally found in adults, and the placenta seems to be an anatomically favourable environment for a sub-population of the parasites. During one particular phase of its lifecycle, the parasite enters the human red blood cells, where it produces proteins that attach themselves to receptor in the wall of the blood vessels. This causes the red blood cells to accumulate in organ capillaries, and gives rise to life threatening symptoms. Adults who have been infected many times can become partly immune, as their defence system gradually starts to recognize the parasite’s proteins. When the placenta is formed, however, a new environment is introduced with a different set of receptors. This means that a new growth niche is made available to a sub-population of the parasites. Earlier studies had suggested that each protein from the parasite attached to only one specific receptor in the placenta. But the natural mechanisms were different from the laboratory studies and therefore the research team collected and analysed placentas on site in Uganda. According to the study, most of the parasites could bind to three different receptors in the placenta and this meant that a future vaccine couldn’t be based on the principle of one protein one receptor, as was previously believed. Website: www.eurekalert.org

Research scientists successfully test new anti-obesity vaccine Scripps Research Institute (SRI) scientists have developed an anti-obesity vaccine that significantly slowed weight gain and reduced body fat in animal models. In the study, mature male rats immunized with specific types of the active vaccine ate normally yet gained less weight and had less body fat, indicating that the vaccine directly affected the body’s metabolism and energy use. This finding may be especially important to stop what is commonly known as yo-yo dieting, the cycle of repeated loss and regain of weight experienced by many dieters. The new vaccine, which is directed against the hormone ghrelin, a naturally occurring hormone that helps regulate energy balance in the body, may mark the effectiveness of immunopharmacotherapy to combat this serious and growing global problem. According to Dr. Kim Janda, Jr., a Chemistry Professor of Chemistry at SRI and Director of the Worm Institute of Research and Medicine, the United States, preventing ghrelin from reaching the central nervous system can produce a desired reduction in weight gain. Ghrelin promotes weight gain and fat storage through its metabolic actions, decreasing the breakdown of stored fat for energy as well as curbing energy expenditure. During periods of weight loss, such as dieting, the body produces high levels of ghrelin to slow down fat metabolism, encourage eating, and promote fat retention, changes that normally make it difficult to lose weight and keep it off. The researchers developed three active vaccines (Ghr1, 2 and 3) to immunize adult male rats. During the study, the rats immunized with Ghr1 and Ghr3 ate normally but, once antibody levels increased, accrued less body weight and fat, indicating an increase in the body’s energy use, a finding supported by studies of genetically altered mice. The study did note, however, that the immunized rats were fed low-energy, low-fat and relatively less palatable chow diets. The study cuationed that whether active immunization against ghrelin would help prevent the development of obesity caused by high-fat ‘Western’ diets or would facilitate weight loss once obesity is established remains uncertain. Website: www.bionity.com

H5N1 and human flu ‘hybrid’ does not spread Researchers from the United States Centre for Disease Control and Prevention created various combinations of the H3N2 human flu virus and H5N1 viruses from Hong Kong, Indonesia and Viet Nam. They tested the ability of the virus to replicate and transmit in ferrets, whose respiratory tract cells interacted with flu viruses similarly to those in humans. Researchers had previously suggested that if these two viruses were able to combine, it could become capable of easily infecting and spreading between people. One study suggested that two proteins on the surface of H5N1 allowed it to attach to and infect bird cells, but were ineffective at attaching to human cells. This led researchers to suggest that H5N1 might need surface proteins more like on those on human flu to trigger a pandemic. The study showed that one virus had human flu proteins on its outer surface, but bird flu genes inside. It was poor at spreading from ferret to ferret though it was good at replicating. A virus with H5N1 external proteins and internal human flu genes replicated as much as normal human flu virus but could not spread between ferrets at all. The researchers said that while the amount of virus that a ferret produced in its nasal cavities might affect the chance of the virus being spread to a nearby animal, other factors in addition to the ability to trigger sneezes could be more important. In the study, ferrets with human flu virus or viruses that had external proteins belonging to the human virus sneezed consistently. Ferrets with any virus with H5N1’s external proteins, however, sneezed rarely or not at all. Website: www.scidev.net

Study finds potential ovarian cancer stem cells Researchers from the Massachusetts General Hospital, the United States, have identified potential ovarian cancer stem cells, which might be behind the difficulty of treating these tumours with standard chemotherapy. According to Dr. Paul Szotek, MGH Pediatric Surgical Research Laboratories, these stem like cancer cells might be resistant to traditional chemotherapy and could be responsible for the ultimately fatal drug-resistant recurrence that is characteristic of ovarian cancer. Recent studies have identified tiny populations of tumor cells that appear to act as stem cells, driving the tumour’s ability to grow and spread. If some of these specialized cells escaped destruction by chemotherapy or radiation, the tumour would be able to recur quickly, often in a form resistant to chemotherapy. Similar cancer cells have been previously identified in leukemia and breast cancer and in cell lines of central nervous system and gastrointestinal tumours. The MGH researchers first examined two mouse ovarian cancer cell lines and identified cells with characteristics of the cancer stem cells found with other tumours. They then observed a small percentage of stem-like cells in human ovarian cancer patients. When mouse ovarian tumour stem-like cells were injected under the skin of mice, they led to the formation of new tumours much faster than did injections of regular tumour cells. Although the potential ovarian cancer stem cells were less responsive than regular tumour cells to in vitro treatment with chemotherapy drug Doxorubicin, the stem-like cells remained sensitive to repeated treatment with Mullerian-inhibiting substance. This protein, important in the normal development of sexual organs, might play a key role in new therapeutic approaches owing to its ability to inhibit the proliferation of tumour cells. Website: www.biosingularity.wordpress.com

Allergies linked to Parkinson’s disease Researchers from Mayo Clinic, the United States, have discovered that allergic rhinitis is associated with the development of Parkinson’s disease later in life. Dr. James Bower, neurologist and lead investigator, said that the association with Parkinson’s disease is increased to almost three times that of someone who does not have allergic rhinitis. Previous studies had shown that regular takers of non-steroidal anti-inflammatory drugs, such as ibuprofen, were less likely to develop Parkinson’s disease. This prompted Dr. Bower’s team to look further into the links between diseases characterized by inflammation and Parkinson’s. They studied 196 people who developed Parkinson’s disease, matched with people of similar age and gender who did not develop Parkinson’s. The researchers examined these groups to determine if those who developed Parkinson’s disease had more inflammatory diseases. They found that those with allergic rhinitis were 2.9 times more likely to develop Parkinson’s. They did not find the same association with Parkinson’s disease in patients with asthma. The investigators theorized that a tendency towards inflammation was the key link between the diseases. According to Dr. Bower, people with allergic rhinitis mounted an immune response with their allergies, so they might be more likely to mount an immune response in the brain as well, which would produce inflammation. The inflammation produced might release certain chemicals in the brain and inadvertently kill brain cells, as seen in Parkinson’s. The study did not prove that allergies caused Parkinson’s disease; instead, it pointed to a link between the two diseases. Thus, allergic rhinitis would now be considered one among many possible risk factors for development of Parkinson’s disease. Website: www.sciencedaily.com