CD44

BARCELONA, Spain I January 17, 2024 I La Merie Publishing released its newest product reviewing the pipeline of anti-GPC3 immunotherapeutics in R&D: GPC3-Targeted Immunotherapy Pipeline Review Target : Glypican 3; GPC3 Product Category : Antibody; Cells; Radiopharmaceuticals; RNA This product provides basic information on immunotherapeutics in R&D targeting GPC33. This product consists of: This product is delivered on the very same day of purchase by e-mail containing competitor and project history reports in pdf format and database credentials. Reports are prepared on the same day. GPC3, a GPI-anchored cell surface heparan sulfate proteoglycan, is an attractive target for hepatocellular carcinoma (HCC) immunotherapy because it is selectively expressed on HCC and promotes HCC cell growth and migration. GPC3 is rarely or not expressed in normal liver tissues, making it a perfect diagnostic and treatment target for HCC. Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. GPC3 has been demonstrated as a viable target for CAR T-cell and NK cell therapy, T-cell engaging bispecific antibodies, immune checkpoint bispecific antibodies, antibody-drug conjugates and radiopharmaceuticals. The report “ GPC3-Targeted Immunotherapy Pipeline Review ” can be acquired at La Merie Publishing’s online store: https://lamerie.com/report/gpc3-targeted-immunotherapy-pipeline-review/ About La Merie Publishing La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. La Merie Publishing prepares brief and full reports. La Merie Publishing products can be purchased in the online store www.lamerie.com and from selected Resellers. La Merie Publishing offers the service of custom report preparation for corporate clients, including, but not limited to, pipeline analysis reports, drug profiles and any other competitive intelligence elaboration of interest. SOURCE: La Merie Publishing

A new cancer therapy attacks tumors by tricking cancer cells into absorbing a snippet of RNA that naturally blocks cell division. A new cancer therapy developed by Purdue University researchers attacks tumors by tricking cancer cells into absorbing a snippet of RNA that naturally blocks cell division. As reported today in Oncogene, tumors treated with the new therapy did not increase in size over the course of a 21-day study, while untreated tumors tripled in size over the same time period. Cancer can begin almost anywhere in the human body. It is characterized by cells that divide uncontrollably and that may be able to ignore signals to die or stop dividing, and even evade the immune system. The therapy, tested in mouse models, combines a delivery system that targets cancer cells with a specially modified version of microRNA-34a, a molecule that acts "like the brakes on a car," slowing or stopping cell division, said Andrea Kasinski, lead author and the William and Patty Miller Associate Professor of biological sciences at Purdue University. In addition to slowing or reversing tumor growth, the targeted microRNA-34a strongly suppressed the activity of at least three genes -- MET, CD44 and AXL -- known to drive cancer and resistance to other cancer therapies, for at least 120 hours. The results indicate that the patent-pending therapy, the newest iteration in more than 15 years of work targeting microRNA to destroy cancer, could be effective on its own and in combination with existing drugs when used against cancers that have built drug resistance. "When we acquired the data, I was ecstatic. I am confident that this approach is better than the current standard of treatment and that there are patients who will benefit from this," said Kasinski, a member of the Purdue Institute for Cancer Research. MicroRNA-34a is a short double strand of ribonucleic acid -- a string of ribonucleic acids attached like the teeth of a zipper along the length of a sugar-phosphate chain. The two strings of the microRNA are unevenly zipped together, with one string acting to guide a protein complex to the worksite in the cell while the other string is destroyed. In healthy cells, microRNA-34a is abundant, but its presence is dramatically reduced in many cancer cells. While the idea of reintroducing microRNA-34a to cancer cells appears simple, the research team had to overcome many challenges in crafting an effective therapy. Naturally occurring RNA breaks down rapidly, so to improve the durability of the therapy, the team stabilized microRNA-34a by adding several small clusters of atoms along the length of the strand. The team modeled its modifications on an FDA-approved chemical structure that researchers at the biotechnology company Alnylam used on similar short interfering RNAs. Experiments on mouse models show the modified microRNA-34a endures for at least 120 hours after being introduced. As a bonus, the fully modified microRNA-34a is invisible to the immune system, which would ordinarily attack double-stranded RNA introduced to the body. To ensure the modified microRNA-34a makes it to cancer cells, the team attached the double strand to a molecule of the vitamin folate. The surfaces of all cells in our body have receptors that bind to folate and draw the vitamin into the cell, but the cells in many cancers -- breast, lung, ovarian and cervical -- have far more folate receptors on their cell surface than do healthy cells. The tiny microRNA-34a and folate compound penetrates the dense tissue of tumors and binds to the folate receptor on the cell surface. It is then drawn inside in a little bag of cell membrane called a vesicle. Once inside the cell, some of the microRNA-34a is able to escape the vesicle and slows cell division. The targeted specificity of the therapy reduces the amount of the compound that must be administered to be effective, which in turn reduces potential toxicity, side effects and cost. The team can also prepare a separate version, which targets a different cell surface receptor, for prostate cancer cells, which do not produce excessive folate receptors. Kasinski and her team are confident in the value of the most recent iteration and will prepare for clinical trials. At Purdue, Kasinski was joined in the research by Philip S. Low, Presidential Scholar for Drug Discovery, Ralph C. Corley Distinguished Professor of Chemistry, and inventor of the FDA-approved drug Cytalux; Nadia A. Lanman, a research assistant professor; Ahmed M. Abdelaal, first author and a graduate student in Kasinski's lab; and researchers Harish Kothandaraman, Kasireddy Sudarshan, Shreyas Iyer and Ikjot S. Sohal. "A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy" was published in Oncogene with support from the National Institutes of Health and the Department of Defense.

The most common cause of hearing loss is progressive because hair cells -- the primary cells to detect sound waves -- cannot regenerate if damaged or lost. Researchers are now getting closer to identifying the mechanisms that may promote this type of regeneration in mammals. Taking a bite of an apple is considered a healthy choice. But have you ever thought about putting in earplugs before your favorite band takes the stage? Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells -- the primary cells to detect sound waves -- cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers). On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience. "We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn't fully understand why," said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells. "This new study tells us how that activation is happening -- a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals," said White. Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene -- ERBB2 -- promoted stem cell-like development by initiating the expression of multiple proteins -- including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration. "When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells," said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. "This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults." "We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal," said White. Additional authors include Daxiang Na, Cameron Baker, and John Ashton, PhD, at the University of Rochester and Medical Center. The research was supported by the U.S. Army Medical Research Mechanism, the National Institute on Deafness and Other Communication Disorders, UR Ventures, and the Schmitt Program on Integrative Neuroscience.