Osaka University

BETHESDA, Md., April 5, 2024 PRNewswire/ -- Precision Biologics, Inc. reports its lead monoclonal antibody, NEO-201, targets circulating human naïve regulatory T cells (Tregs) in both healthy donors and cancer patients. A poster presentation discussing this data will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, at the San Diego Convention Center in San Diego, CA on April 8th, 2024. Poster title: The O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) NEO-201 can also target human regulatory T cells (Tregs) This study was performed by Drs. Atsushi Tanaka and Shimon Sakaguchi from Osaka University, Japan. Dr. Sakaguchi's group independently analyzed by flow cytometry the ability of NEO-201 to recognize naïve Tregs in peripheral blood mononuclear cells (PBMCs) from healthy donors, confirming findings from Precision Biologics in PBMCs from cancer patients. Previous studies performed by Precision Biologics have shown that approximately 4.6% of CD4+ T cells express NEO-201 target antigen and that those CD4+ T cells have Tregs phenotype. In addition, in a recently published phase 1 clinical study it has been observed that NEO-201 binds to CD4+/ CD25+/, CD127-/, Foxp3+/, CD15s+ cells from PBMCs from cancer patients with solid tumors. The purpose of this study performed in Dr. Sakaguchi's laboratory was to corroborate and further characterize the phenotype of the specific subset of CD4+ T cells expressing the NEO-201 target antigen. In this study, human PBMCs were collected from 7 healthy donors (HD) at Osaka University and 6 cancer patients from Precision Biologics ongoing phase II clinical trial (Clinical Trial NCT03476681) evaluating the efficacy of the combination of NEO-201 with pembrolizumab in adults with solid tumors resistant to checkpoint inhibitors. Phenotypic analysis was conducted by flow cytometry to evaluate which fraction of CD4+ T cells is recognized by NEO-201. Flow cytometry analysis revealed that NEO-201 recognizes fraction I of CD4 T cells in both healthy donors and cancer patients. Fraction I includes naïve Tregs (nTregs) with the following phenotype: CD3+/CD4+/CD45RA+/Foxp3low cells. The percentage of nTregs in cancer patients was higher than the percentage detected in healthy donors. On the other hand, this study revealed that NEO-201 does not bind to fraction II of CD4 T cells in both healthy donors and cancer patients. Fraction II includes effector Tregs (eTregs) with the following phenotype: CD3+/CD4+/CD45RA-/Foxp3high cells. When subjected to t-cell receptor (TCR) stimulation, nTregs undergo proliferation and differentiate into eTregs, which can then infiltrate into tumor microenvironment (TME) and induce suppression of anticancer immunity. Depletion of circulating NEO-201 positive nTregs in cancer patients after NEO-201 treatment may prevent the differentiation of nTregs into eTregs, thus reducing their accumulation in the TME. This study suggests therapy with NEO-201 may reduce Treg-mediated suppression of anticancer immunity. The poster will be presented in person at the San Diego Convention Center, San Diego, CA, on Monday April 8th, 2024. Please stop by poster # 2716 at Poster Section 6, Poster Board number 7 (1.30 p.m.–5.00 p.m.). About Precision Biologics Founded in 2012, Precision Biologics, Inc. is a clinical stage biotechnology corporation focused on developing therapeutic and diagnostic products for the detection and treatment of cancer. The company's antibody drug candidates and diagnostics are designed to detect and target the tumor with minimal damage to healthy cells. Precision Biologics is uniquely positioned to create innovative therapeutics through the use of proprietary cancer vaccines, several of which have demonstrated success in human trials. By marrying this platform with today's breakthrough technologies, the company is developing antibody therapeutics that could change the way we detect and treat cancer. For more information on Precision Biologics, please visit .

Researchers have conducted a series of participatory deliberation workshops in which the participants were asked to consider issues of future society and manufacturing, in general, and as they relate to hydrothermally produced porous glass. In workshops where the perspective of 'imaginary future generations' was adopted, participants' perceptions of the technology's feasibility and future potentiality changed significantly. The world approaches an environmental tipping point, and our decisions now regarding energy, resources, and the environment will have profound consequences for the future. Despite this, most sustainable thought tends to be limited to the viewpoint of current generations. In a study published in Technological Forecasting and Social Change, researchers from Osaka University have revealed that adopting the perspective of "imaginary future generations" (IFGs) can yield fascinating insights into long-term social and technological trends. The researchers organized a series of four workshops at Osaka University, with participants drawn from the faculty and student body of the Graduate School of Engineering. The workshops discussed the state of future society and manufacturing in general, and also looked at one technology in particular: hydrothermally produced porous glass. During the workshops, the participants were asked to think about this technology from the perspective of IFGs, to imagine how this technology might be adopted in the future and to assess its future potentiality. "We chose hydrothermally produced porous glass for the case study because of the generational trade-offs involved," says lead author of the study Keishiro Hara. "Porous glass is incredibly useful as either a filter for removing impurities or an insulator for buildings. Also, it can be recycled into new porous glass more or less indefinitely. The problem is that making it takes a lot of energy -- both to pulverize waste glass and to heat water to very high temperatures. There's a striking trade-off between costs now and gains in the future." In the workshops, the participants first looked at issues involving society and manufacturing from the perspective of the present and were then asked to imagine themselves in the shoes of their counterparts in 2040. "The future the participants imagined was quite different from the future as seen from the perspective of the current generation," explains Toshihiro Tanaka, senior author. "Most groups described a future in which sustainability has become a central concern for society. Meanwhile, advances in renewal energy mean that energy is abundant, as are resources, as frontiers such as the moon and deep ocean are opened to exploration. In this context, hydrothermally produced porous glass comes into its own as a sustainable way to recycle glass, and the energy needed to produce it is readily available." The participants were surveyed between workshops and asked to rank indicators related to the future potentiality of the technology. Interestingly, these rankings looked quite different after the workshops in which the participants were asked to take on the perspective of "imaginary future generations." "We noticed that when the "imaginary future generations" method, which has been proven to be effective in facilitating long-term thinking, was adopted, participants perceived the feasibility of this technology differently, and their adoption scenarios changed accordingly," says Hara. The study suggests that the simple act of putting ourselves in the position of future generations may provide new perspectives on issues of sustainability and technology, helping us to rethink our priorities and set new directions for research and development.

Researchers discovered a mechanism behind middle-age obesity in rat brains. They believe that a similar mechanism exists in humans as well. This discovery may lead to improvements in preventing obesity and metabolic syndrome. Nagoya University researchers and their colleagues in Japan have found that middle-age obesity is caused by age-related changes in the shape of neurons in the hypothalamus, a region of the brain that controls metabolism and appetite. A protein called melanocortin-4 receptor (MC4R) detects overnutrition and regulates metabolism and appetite to prevent obesity. According to their study in rats, MC4Rs were concentrated in primary cilia (antenna-like structures) that extend from a couple of groups of hypothalamic neurons. The study also showed that the primary cilia became shorter with age, which decreased MC4Rs accordingly, resulting in weight gain. "We believe that a similar mechanism exists in humans as well," said Professor Kazuhiro Nakamura of the Nagoya University Graduate School of Medicine, the lead author of the study. "We hope our finding will lead to a fundamental treatment for obesity." The researchers published the results of the study in the journal Cell Metabolism. As we get older, we become more prone to being overweight and obesity. Obese people are more susceptible to diabetes, hyperlipidemia, and other chronic diseases. Previous studies have suggested that middle-age weight gain is caused by a decline in overall metabolism due to aging, but the mechanism was unclear. A research team of the Nagoya University Graduate School of Medicine, in collaboration with researchers from Osaka University, the University of Tokyo, and the Nagoya University Research Institute of Environmental Medicine, conducted a study focusing on MC4Rs. MC4Rs stimulate metabolism and suppress food intake in response to an overeating signal from melanocortin. Initially, the research team examined the distribution of MC4Rs in the rat brain by utilizing an antibody they had developed specifically to make MC4Rs visible. They found that MC4Rs are present exclusively in primary cilia of specific groups of hypothalamic neurons. The team next investigated the length of the primary cilia that had MC4Rs (MC4R+ cilia) in the brains of 9-week-old (young) rats and 6-month-old (middle-age) rats. The team found that MC4R+ cilia in middle-aged rats were significantly shorter than those in young rats. Accordingly, the metabolism and the fat-burning capacity of middle-aged rats were much lower than those of young rats. The team next analyzed MC4R+ cilia in rats under different dietary conditions. The results showed that MC4R+ cilia in rats on a normal diet gradually shortened with age. On the other hand, MC4R+ cilia in rats on a high-fat diet shortened at a faster pace, while those in rats on a restricted diet shortened at a slower pace. Interestingly, the team also found that MC4R+ cilia that once disappeared with age were regenerated in rats raised under two months of dietary restriction. In the study, the team also used genetic technologies to make MC4R+ cilia shorter in young rats. These rats showed increased food intake and decreased metabolism, leading to weight gain. The team also administered a hormone called leptin to the brains of rats with artificially shortened MC4R+ cilia. Leptin is thought to help reduce food intake. Surprisingly, however, their appetite was not reduced, indicating that leptin could not exert anti-obesity effects. "This phenomenon, called leptin resistance, is often observed in obese human patients as well. This is an obstacle to the treatment of obesity, but the cause has long been unknown," explained Dr. Manami Oya, the first author of the study. "In obese patients, adipose tissue secretes excessive leptin, which triggers the chronic action of melanocortin. Our study suggests that this may promote the age-related shortening of MC4R+ cilia and put animals into a downward spiral where melanocortin becomes ineffective, increasing the risk of obesity." The study concluded that the age-related shortening of MC4R+ cilia causes middle-age obesity and leptin resistance in rats. The researchers demonstrated that dietary restriction is one method to prevent and treat overweight and obesity. Prof. Nakamura said, "Moderate eating habits could maintain MC4R+ cilia long enough to keep the brain's anti-obesity system in good shape even as we age."