1. Nat Biotechnol: Edible antibody molecules contribute to the treatment of gastrointestinal diseases
Therapeutic antibodies are increasingly used clinically to treat a variety of diseases. However, oral gut-targeted antibodies remain a challenge because they cannot survive digestion and reach gastrointestinal tissue. Now, scientists have developed a new antibody technology that combines the advantages of antibody-based therapy with the convenience of oral administration. Importantly, these antibodies are produced directly from yeast in the food production process. The work is published in the Nature Biotechnology. The injection of conventional therapeutic antibodies into the bloodstream to treat or prevent a variety of diseases is widely used, but these antibody-based therapies are not designed for oral intake in the gut, as the digestive environment of the gastrointestinal tract may decompose them.
(doi: 10.1038/s41587-019-0070-x)
2. Science: A novel antibody-binding drug for the treatment of neuroblastoma
Medical scientists at Children’s Hospital of Philadelphia (CHOP) have developed an effective antibody-based treatment targeting the surface proteins of neuroblastoma in most children, which can effectively kill cancer cells. The results of the study were recently published in the Science Translational Medicine. “In 2008, we found that anaplastic lymphoma kinase (ALK) mutation was the cause of most hereditary neuroblastoma, and that it was found in 14 per cent of the most malignant patients. This indicates that ALK is a therapeutic target for neuroblastoma, which provides a basis for us to develop ALK inhibitory therapy. We now find that non-mutated ALK is also present in most glioblastoma, which provides us with the opportunity to treat most patients through targeted ALK.” The lead author of the study, a pediatric oncologist at CHOP, Dr. Yael Moss é said. Neuroblastoma is a pediatric cancer that occurs in the developing peripheral nervous system. It usually causes solid tumors in the chest and abdomen of children, which is the most common childhood cancer, resulting in more than 10% of cancer-related child deaths. Even with continuous treatment, children with malignant neuroblastoma have a poor prognosis.
Schematic illustration of the CDX-0125-TEI molecule. (doi: 10.1126/scitranslmed.aau9732)
3. Science: Reveal a new antibody therapy that prevents cytomegalovirus reactivation after bone marrow transplantation
In a new study, scientists from the Queensland Institute of Medicine in Australia used a newly developed mouse model to challenge the long-standing view of why a common cytomegalovirus (CMV) can be reactivated in humans with impaired immune systems and lead to life-threatening infections. The findings pave the way for cheaper and safer treatments to protect patients from CMV and it is a big problem in the field of bone marrow transplantation. “Our study is the first to show that antibodies can play a leading role in controlling CMV reactivation, which is a complete reversal of dogma. Previous studies on CMV reactivation have focused on T cells. Occasionally, it has been suggested that antibodies produced by B cells in the immune system play a role in the resistance to CMV, but it seems to be a supportive role.” Hill said, “clinical trials using antibodies against the virus have yielded disappointing results.”
4. PNAS: A new antibody therapy for cancer
Recently, researchers from Medical Center of Rush University found that specific cancer molecules can use protein molecules in the body’s immune system to delay death. The researchers also found that antibodies neutralized such molecules could kill tumor cells and further reduce the size of the tumor in mice. The results are published in the PNAS. This discovery will provide new hope for cancer immunotherapy in recent years. Dr Kalipada Pahan, a professor at Rush University and author of the study, said it was a new direction in the treatment of cancer. One of the main reasons why cancer is difficult to cure is that cancer cells break the normal life cycle, that is, the process of apoptosis. By analyzing blood samples from patients with prostate cancer, as well as cancer cells from human and mouse, the authors hope to find out the mechanism by which cancer cells escape death.
(doi: 10.1073/pnas.1705536114)
5. Cell Host Microbe: Experimental antibody cocktail therapy can be used to treat Ebola virus infection
Recently, scientists developed a combination of monoclonal antibodies (mAb) to protect animals from three Ebola viruses known to cause human diseases. Two representative articles were published in the recent Cell Host Microbe. The monoclonal antibody cocktail therapy called MBP134 is the first treatment to protect monkeys from the Ebola virus, as well as the Sudanese and Bundibugyo viruses, and can produce a wide range of effectiveness. The development of a single treatment that could be used for patients with all different types of Ebola virus is a significant step forward in this area. This discovery not only has an impact on the treatment of the Sudanese virus and Bundibugyo virus, and it has an impact on the emerging Ebola virus. The study cites growing evidence that monoclonal antibodies can be used to treat even the deadliest infections.
(doi: 10.1016/j.chom.2018.12.004)
6. The first DNA-encoded monoclonal antibody therapy is expected to enter clinical trials
Recently, the Wesda Institute and Inovio Pharmaceuticals jointly announced that FDA has approved their first human clinical trial to investigate the safety and tolerance of a new synthetic DNA encoded monoclonal antibody (DMAb) therapy in the prevention of Zika virus infection. Unlike all known conventional therapeutic antibodies, DMAb is made in the human body rather than in factories, and patients are given DNA instructions to equip their bodies with the necessary tools. Thus, highly specific antibodies are produced to target pathogenic targets, such as bacteria, virus-infected cells and cancer cells. “DMAb technology can change the clinical story we know. Over the past few years we have conducted very detailed preclinical research and developed some new platforms. At the same time, CELLECTRA transfer system is used to produce DMAbs, in vivo, which has more development potential than the traditional monoclonal antibody method. It can also expand the therapeutic strategy and open up a new market for the prevention of diseases and the development of new therapies in the future.” David B. Weiner, the researcher, said.
7. Nat Commun: Human antibody is expected to treat fungal infection
A new study in the Nature Communications suggests a new way to diagnose, treat and prevent invisible fungal infections, providing new solutions to important diseases that affect more than 1.5 million people worldwide each year. In addition to causing more than 100 million sore infections a year, the fungus is one of the most life-threatening blood infections in developed countries. Despite the advances in public health, many people infected with fungi in the blood will inevitably die, even if they can be identified and treated with antifungal drugs. These treatments themselves are often ineffective, and more infections are becoming resistant to the treatment of some front-line antifungal drugs. Recently, the Center for Medical Mycology at the University of Aberdeen was the first to successfully use fungal Candida antibodies cloned from patients. This new cloned antibody has successfully protected animals from Candida blood infection and demonstrated its potential in the treatment and diagnosis of Candida infection.
Generation of human monoclonal antibodies from single B cells. (doi: 10.1016/j.chom.2018.12.004)
8. Immunity: Breakthrough! New antibodies are expected to treat many types of cancer
In a recent study published in Immunity, scientists from the University of Southampton have developed a new antibody that may help unravel the mysteries of the body’s immune system against cancer. In this article, the researchers engineered the antibody to target immune receptor 4-1BB, which activates killer T cells to find and destroy cancer cells. 4-1BB is a target of immunotherapy, which mainly exists on regulatory T cells in tumors that can shut down the function of killer T cells. At the same time, killer T cells can also express 4-1BB, but the expression degree is low. In preclinical tumor models, the researchers set up a 4-1BB antibody that removes regulatory T cells and promotes tumor regression. Because the antibody is very good at removing regulatory T cells and not at stimulating killer T cells, it seems impossible for researchers to use such regular antibodies to regulate the treatment of the disease.
(doi: 10.1016/j.immuni.2018.09.014)
9. Science: The new four-in-one antibody is expected to help humans resist the infection of a variety of influenza viruses
In a recent study published in Science, scientists from institutions such as the Scripps Institute in the United States have developed a new four-in-one antibody strategy against influenza virus infection. In this article, the researchers described how they developed the new antibody and tested it in mice. Although researchers have done a lot of research over the years, the flu virus still infects a lot of people around the world every year, causing about 500000 deaths a year. At present, the way to prevent people from contracting the influenza virus is to produce seasonal influenza vaccines every year and vaccinate the population as much as possible. Although vaccines can help many people effectively resist viral infections, they still fail to protect some vulnerable people, such as the elderly, and provide the body with only one type of influenza virus. Thus, scientists need to keep looking for a better way to fight the flu virus, and for that reason, in this study, researchers have developed a new type of antibody. It can effectively resist many types of influenza viruses and is expected to help people prevent influenza throughout the influenza season in the future.
10. Ange Chem Int Ed: Special nanobodies in alpaca may be effective against a range of cancers
Nature often provides answers to unsolved medical problems, such as the alpaca’s immune system, which may be able to solve the problems or challenges posed by cancer to humans. Recently, in a study published in the Angewandte Chemie International Edition, scientists from the Barcelona Institute of Biomedical Research and the Free University of Brussels have described a range of therapeutic tools that are expected to block epidermal growth factor (EGF) activity, a growth factor that is dysfunctional in cancer cells and a therapeutic target for cancer. So far, researchers have not found inhibitors that block EGF function. In this study, for the first time, researchers have found a nanobody family of (nanobodies) from alpacas which is endemic to camels. The antibodies are effective against EGF, and the researchers describe the molecular mechanisms behind the selectivity and affinity of these nanobodies. Researcher Monica Varese explains that although researchers have made some progress in developing treatments to resist EGFR (EGF receptors) in patients, the effectiveness of these treatments will gradually decline as drug resistance develops in patients. By using advanced biotechnology tools (nanobodies), theye can synthesize a high-affinity antibody inhibitor for EGF.