Hunan University

Immunotherapies for cancer aim to induce the immune system to combat cancer cells more effectively. A research team has now described a new, modular strategy for T-cell-based immunotherapy that manages to work without complex genetic modifications. Modulation of cell-cell communications through an ingenious regulatory circuit using various small, specially folded DNA molecules (aptamers) causes cancer cells to directly activate their mortal enemies, T cells. Immunotherapies for cancer aim to induce the immune system to combat cancer cells more effectively. In the journal Angewandte Chemie, a Chinese research team has now described a new, modular strategy for T-cell-based immunotherapy that manages to work without complex genetic modifications. Modulation of cell-cell communications through an ingenious regulatory circuit using various small, specially folded DNA molecules (aptamers) causes cancer cells to directly activate their mortal enemies, T cells. For multicell organisms like our bodies to function correctly, the cells must "coordinate" with each other. In this complex communications network, signals are sent and received, processed, and passed on. The regulation of specific membrane receptors that bind to signal molecules plays an important role in this process. In a typical example, components of the immune system, known as antigen-presenting cells (APCs), sense the presence of cancer antigens. They transmit the signal to lymph nodes, in which specific T cells are activated by their receptors, move into the bloodstream, and kill the cancer cells. Unfortunately, cancer cells use a variety of "loopholes" to escape the immune system. The team at Hunan University, Hangzhou Institute of Medicine, the Chinese Academy of Sciences, and Shanghai Jiao Tong University is working on ways to close these loopholes. Their goal is to establish new cellular interactions without having to produce genetically modified immune cells or receptors. The idea is to produce a "short circuit" in the communication pathways, by which the T cells are activated directly by the tumor cells, avoiding the detour through APCs. Led by Weihong Tan and Liping Qiu, the team developed a "regulatory circuit" consisting of two modules: 1) "recognition-then-triggering" and 2) "aggregation-then-activation." The circuit is based on different DNA aptamers -- short DNA segments that fold into a "preprogrammed" 3D structure and "recognize" specific target molecules. The DNA for module 1) is initially inactive and partially paired into a double strand. If cancer cells are present, the aptamer portion of the "recognition" single strand binds to protein tyrosinase kinase 7, a protein found in large numbers on the surface of many cancer cells. This splits the DNA double strand, releasing the "triggering strand," which triggers module 2). Module 2) requires two more types of aptamer. Both specifically bind to CD28 immunoreceptors on the surfaces of T cells. CD28 is a co-stimulator in the activation of T cells. This triggering strand binds to an additional "loop" on a type 1 aptamer. The loop opens and the newly released end binds to a type 2 aptamer, which then binds another type 1 aptamer, and so on (hybridization). This results in a double strand and the bound CD28 receptors aggregate, triggering a signal cascade that massively amplifies the activation of T cells. In this way, "short-circuited" cell communication causes cancer cells to very effectively directly induce T cells to kill them.

A new universal flu vaccine protects against influenza B viruses, offering broad defense against different strains and improved immune protection, according to a new study. A new universal flu vaccine protects against influenza B viruses, offering broad defense against different strains and improved immune protection, according to a new study by researchers in the Institute for Biomedical Sciences at Georgia State University. The double-layered protein nanoparticle vaccine, which is constructed with a stabilized portion of the influenza virus (the hemagglutinin (HA) stalk), induced broadly reactive immune responses and conferred robust and sustained cross-immune protection against influenza B virus strains of both lineages. The findings are published in the journal Biomaterials. Influenza epidemics pose a major threat to public health, and type B influenza has coincided with several severe flu outbreaks. About one-fourth of clinical infection cases are caused by influenza B viruses each year. Influenza B viruses are sometimes the dominant circulating strains during influenza seasons, such as the 2019-20 U.S. flu season when influenza B caused more than 50 percent of the infections. Influenza B has two lineages that are genetically distinct and trigger different immune responses. Seasonal flu vaccines are developed with one or both lineages of influenza B viruses, but they're limited by the ability of circulating strains to escape the immune system or vaccination. These vaccines are often ineffective because the variable portion of the influenza virus (the HA head) evolves. As a result, seasonal influenza vaccines need to be reformulated and updated frequently. To overcome these limitations, a universal influenza vaccine containing conserved parts of the virus and providing substantial broad cross-protection against diverse virus strains is urgently needed. "In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates," said Dr. Baozhong Wang, senior author of the study and Distinguished University Professor in the Institute for Biomedical Sciences at Georgia State University. "We found that layered protein nanoparticles incorporated with structure-stabilized constant antigens have potential as a universal influenza vaccine with improved immune protective potency and breadth." The nanoparticle vaccine was tested in cell culture and in mice. Studies in cell culture found the protein nanoparticles were effectively taken up to activate dendritic cells, which are critical for inducing protective immune responses against pathogens. The vaccine was found to be safe, biocompatible, biodegradable and highly immunogenic in animals. "Our next aim is to combine the influenza A nanoparticles from our previous study with the influenza B nanoparticles we have fabricated and tested here to create a multivalent universal influenza nanoparticle vaccine against both influenza A and B," Wang said. Co-authors of the study include Yufeng Song (first author), Wandi Zhu, Ye Wang, Lei Deng, Yao Ma, Chunhong Dong, Gilbert X. Gonzalez, Joo Kim, Lai Wei, Sang-Moo Kang and Bao-Zhong Wang of the Center for Inflammation, Immunity & Infection in the Institute for Biomedical Sciences at Georgia State. Deng is also affiliated with Hunan University in Changsha, China. The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

A University of Florida chemistry professor who fled the United States after falling under investigation for his ties to academic institutions in China has been at the forefront of developing a diagnostic test for the novel coronavirus in China. A University of Florida chemistry professor of Chinese heritage who fled the United States after falling under investigation for his ties to academic institutions in China has been at the forefront of developing a diagnostic test for the novel coronavirus in China. Weihong Tan left the United States and his position in Gainesville, Florida to take a post at Hunan University in south-central China, where he continues with his research. Tan fell under federal scrutiny for his alleged failure to disclose financial ties to academic institutions in China while he worked at the University of Florida and received significant grant funding from the National Institutes of Health, ProPublica reported. Since moving to China, Tan helped lead that nation’s response to the novel coronavirus pandemic that has spread across the globe. Financially supported by a grant from the Chinese government, Tan shifted his research from cancer and focused on the escalating coronavirus epidemic. He and his colleagues from other Chinese academic institutions developed a diagnostics kit that provides results in less than an hour and can be used in either a physician’s officer or in less controlled, non-medical environments, ProPublica reported. In his interview with ProPublica, Tan did not provide much information on the diagnostics test for the coronavirus, which has now infected more than 236,384 people across the globe. Multiple companies have been focused on the development of diagnostics for the pandemic, with a few already approved by the U.S. Food and Drug Administration under Emergency Use Authorization. Last week, the FDA approved Roche’s cobas SARS-CoV-2 Test under EUA and this week, Abbott’s RealTime SARS-CoV-2 test was approved under EUA. Abbott said it has plans to immediately ship more than 150,000 units and more are coming online. The FDA also approved a system by Thermo Fisher Scientific under the EUA. Tan was one of the U.S.-based researchers who had taken part in China’s Thousand Talents Plan , which provides funding for scientists willing to conduct scientific research on behalf of the Chinese government. During his nearly two decades at the University of Florida, Han had also been able to teach part time at the University of Hunan, ProPublica noted. Florida began to look into Han’s activities following an alert from the National Institutes of Health, ProPublica reported. During an interview with Tan, the noted researcher provided documentation that showed the U.S. college was aware of his work with the Chinese university for years. The U.S. government has been closely monitoring researchers with ties to China, either through funding or heritage. A 2017 report issued by the FBI noted that that intellectual-property theft by China costs the U.S. as much as $600 billion annually. The U.S. government has alleged that the Chinese Thousand Talents program is not only a way for that country to prosper off of U.S.-based research but also as a means to steal proprietary information from companies and research institutions. Last year, the Chinese government tamped down promotion of the Thousand Talents plan as western fears mounted over concerns of intellectual property theft. Tan isn’t the only researcher based in the United States to face intense scrutiny over the connections with Chinese institutions. Last year, researchers at Emory University and at MD Anderson were terminated following the revelation of potential undisclosed funding ties with the government of China. Earlier this year, the government charged Harvard University’s Charles Lieber was charged with “one count of making a materially false, fictitious and fraudulent statement” regarding his work with organizations tied to the Chinese government, including the Thousand Talents Plan, while he filed for research grant funding from the National Institutes of Health.