BLNK

该研究结果表明circRNA_0013936有望成为BCa的有效治疗靶点。这些发现为膀胱癌的临床治疗提供了理论依据和新思路。 膀胱癌 (BCa)是泌尿系统常见的恶性肿瘤，侵袭性膀胱癌患者预后较差。多形核骨髓源性抑制细胞(PMN-MDSCs)是一种病理性活化的免疫细胞，具有很强的免疫抑制功能，出现在许多疾病中。PMNMDSCs浸润肿瘤微环境是肿瘤进展和免疫治疗效果不佳的主要原因之一，其存在与预后不良显著相关。尽管近年来PMN-MDSCs的调控机制研究取得了一些进展，但PMN-MDSCs的病理活化机制仍在很大程度上是未知的，这限制了对这些细胞的选择性靶向。 图片来源：https://doi.org/10.1186/s12943-024-01968-2 近日，来自南方医科大学的研究者们在Mol Cancer.杂志上发表了题为“Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs”的文章，该研究表明circRNA_0013936有望成为BCa的有效治疗靶点。 PMN-MDSCs是肿瘤免疫耐受和肿瘤免疫治疗失败的原因之一。本研究发现，膀胱癌(BCa)源性外泌体circRNA_0013936可通过调节脂肪酸转运蛋白2 (FATP2)和受体相互作用蛋白激酶3 (RIPK3)的表达，增强PMN-MDSCs的免疫抑制活性。然而，潜在的机制在很大程度上仍然未知。 bca来源的外泌体被分离并用于一系列实验。研究者通过RNA测序用于鉴定差异表达的环状RNA，通过Western blotting、免疫组织化学、免疫荧光、qRTPCR、ELISA和流式细胞术等方法揭示circRNA_0013936促进PMN-MDSC免疫抑制活性的可能机制。 bca来源外泌体中富集的CircRNA_0013936可促进PMN-MDSCs中FATP2的表达，抑制RIPK3的表达。机制上，circRNA_0013936通过海绵分别直接靶向JAK2和CREB1的miR-320a和miR-301b促进了FATP2的表达，抑制了RIPK3的表达。最终，在PMN-MDSCs中，circRNA_0013936通过circRNA_0013936/miR-320a/JAK2通路上调FATP2，并通过circRNA_0013936/miR-301b/CREB1通路下调RIPK3，从而显著抑制CD8+ T细胞的功能。 PMN-MDSCs通过过表达FATP2和低表达RIPK3浸润肿瘤微环境 图片来源：https://doi.org/10.1186/s12943-024-01968-2 总之，本研究发现bca来源的外泌体circRNA_0013936通过circRNA_0013936/miR-320a/JAK2通路海绵化miR-320a上调FATP2，通过circRNA_0013936/miR-301b-3p/ CREB1通路海绵化miR301b-3p下调RIPK3，最终促进免疫抑制分子的合成，严重抑制CD8+T细胞的功能和CD8+T细胞分泌IFN-γ。该研究结果表明circRNA_0013936有望成为BCa的有效治疗靶点。这些发现为膀胱癌的临床治疗提供了理论依据和新思路。（生物谷 Bioon.com） 参考文献 Xiaojun Shi et al. Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs. Mol Cancer. 2024 Mar 9;23(1):52. doi: 10.1186/s12943-024-01968-2.

BEVERLY, Mass.--(BUSINESS WIRE)-- Akston Biosciences, dedicated to accelerating the next revolution in Animal Health, announced the publication in Frontiers in Immunology of a study on AKS-107, an innovative antigen-specific immunotherapy based on Akston's Ambifect® Fc-fusion protein platform. The study demonstrated AKS-107's potential to target and delete insulin-specific B cells, which are implicated in the development of Type 1 Diabetes (T1D). Fc-fusion proteins based on this platform can be designed to interact only with parts of the immune system related to the target disease while minimizing off-target effects. AKS-107 is a human IgG1 Fc-fusion protein engineered to retain conformational insulin epitopes that bind to B cell receptors while preventing binding to the insulin metabolic receptor. The study conducted in non-obese diabetic (NOD) mice and insulin-reactive B cell receptor transgenic mouse strains showed that AKS-107 can safely prevent spontaneous diabetes, demonstrating durable immune tolerance. Studies have shown that AKS-107 has a protracted pharmacokinetic pro was well-tolerated in both mice and non-human primates, making it a promising candidate for clinical development in T1D prevention settings. "Akston has confirmed the versatility of the Ambifect® platform across diverse treatment areas, including extended duration insulin therapies, infectious disease vaccines, and, with AKS-107, interrupting an autoimmune cascade," said Todd Zion, Ph.D., President & CEO of Akston Biosciences. “We are now exploring its application to therapeutic vaccination, where the immune system is recruited to target proteins involved in non-communicable diseases," he added. “Using a common platform allows Akston to reduce development time and manufacturing costs across its entire pipeline.” As part of its renewed focus on Animal Health, Akston recently spun out all applications for human T1D prevention and treatment, including AKS-107 for disease prevention and AKS-440, its once-a-week basal insulin therapy. Akston also spun out all human clinical vaccine applications with lead candidates targeting misfolded proteins involved in neurodegenerative diseases including Alzheimer’s and infectious diseases including Middle East Respiratory Syndrome (MERS) and Dengue fever. Regarding its Animal Health applications, Akston is partnered with Dechra Pharmaceuticals PLC to commercialize canine and feline ultra-long insulins. The company is also advancing lead therapeutic vaccines against nerve growth factor for chronic pain and IL-31 for atopic dermatitis. About Akston Biosciences: Akston Biosciences Corporation is dedicated to accelerating the next revolution in Animal Health by inventing, developing, and manufacturing breakthrough protein therapeutics for veterinary use. Its vertically integrated capabilities, including a kilogram-scale cGMP manufacturing facility dedicated to Animal Health, can significantly reduce the time and cost from discovery to commercial introduction. Akston leverages its Ambifect® Fc-fusion protein platform to create innovative, extended-duration biologics and therapeutic vaccines. Its facilities are located in Beverly, Mass. Additional information is available at akstonbio.com.

Nurix and Seagen to develop a portfolio of Degrader-Antibody Conjugates (DACs): antibodies that deliver a targeted protein degrader payload to selectively kill cancer cells Nurix to receive a $60 million upfront payment, in addition to the potential for approximately $3.4 billion in milestone payments plus future royalties Nurix retains an option for U.S. profit sharing and co-promotion on two products arising from the collaboration Nurix to host a conference call today, September 7 at 8:30 a.m. ET Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, today announced that it has entered into a multi-year, multi-target strategic collaboration agreement with Seagen Inc. to advance a new class of medicines called Degrader-Antibody Conjugates (DACs) for use in cancer. The collaboration between the two companies will focus on an innovative approach to combine two powerful technologies to target cancer—antibody-drug conjugation (ADC) and targeted protein degradation (TPD)—with the goal of creating drugs with new mechanisms of action as well as improved specificity and anti-cancer activity. “By combining the tissue and tumor specificity of antibodies with highly potent and catalytic targeted degradation of cancer driver proteins, we believe that DACs may represent a next generation of cancer medicine for a wide range of solid tumors and hematologic malignancies,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “With Seagen, our strategic goal is to advance ADC technology to the next level to provide patients with new DAC drugs that deliver greater anti-tumor efficacy and safety compared to currently available agents.” “The targeted protein degrader modality provides unique advantages over payloads currently employed across the ADC field,” said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. “This collaboration is a new application of our DELigase technology, and we are delighted to work with Seagen, a pioneer in the development and commercialization of ADC therapeutics, to create a new generation of drugs to fight cancer.” Under the terms of the agreement, Nurix will receive an upfront payment of $60 million and has the potential to receive up to approximately $3.4 billion in research, development, regulatory and commercial milestone payments across multiple programs. In addition, Nurix will be eligible for mid-single to low double digit tiered royalties on future sales, and Nurix retains an option for U.S. profit sharing and co-promotion on two products arising from the collaboration. As part of the multi-year collaboration, Nurix will use its proprietary DELigase platform to develop a suite of targeted protein degraders against multiple targets nominated by Seagen that are suitable for antibody conjugation. Seagen will be responsible for conjugating these degraders to antibodies to make DACs and advancing these DAC drug candidates through preclinical and clinical development and commercialization. Given the potential to conjugate multiple antibodies to unique degraders, several DAC drugs may be developed and commercialized within this collaboration. With the receipt of the $60 million upfront payment, Nurix expects that its existing cash, cash equivalents and marketable securities, excluding any future potential milestones from collaborations, will be sufficient to fund its operating activities into the second quarter of 2025. About Nurix Therapeutics, Inc. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative medicines based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com. The content above comes from the network. if any infringement, please contact us to modify.