You-Tong Wu, Yan Fang, Qi Wei, Heping Shi, Huiling Tan, Yafang Deng, Zhiqun Zeng, Jian Qiu, Chuo Chen, Lijun Sun, Zhijian J Chen
The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models...
December 6, 2022: Proceedings of the National Academy of Sciences of the United States of America
Zhiyu Zhao, Shuming Dong, Yue Liu, Jianxin Wang, Li Ba, Cong Zhang, Xinyu Cao, Changjun Wu, Piaoping Yang
Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state in the tumor microenvironment (TME), the therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB therapy to kill tumors efficiently. The tumor cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnO x ) nanozyme termed [email protected] showed intrinsic peroxidase and oxidase-like activities in an acidic TME...
November 28, 2022: ACS Nano
Robin Hallett, Ester Bonfill-Teixidor, Raffaella Iurlaro, Alexandra Arias, Swetha Raman, Peter E Bayliss, Olga Egorova, Almudena Neva-Alejo, Aj Robert McGray, Esther Lau, Alexandre Bosch, Melissa Beilschmidt, Dorothea Maetzel, Johan Fransson, Isabel Huber-Ruano, Judit Anido, Jean-Philippe Julien, Patricia A Giblin, Joan Seoane
PURPOSE: Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target. EXPERIMENTAL DESIGN: We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression...
November 28, 2022: Clinical Cancer Research
Xuanxuan Li, Kuo Kang, Yuanhao Peng, Lin Shen, Liangfang Shen, Yangying Zhou
The Regulator of Chromosome Condensation 2 (RCC2) is an important gene that regulates mitosis and cytoplasmic division in the cell cycle. Although there have been reported in several individual tumors, an integrative analysis of RCC2 and its clinical significance across diverse cancer types is poorly elucidated. In this study, we performed integrative bioinformatics analyses to profile the expression landscape and assess the prognostic value of RCC2 in pan-cancers. Correlations between RCC2 expression and tumor-infiltrating immune cells, tumor mutation burden (TMB), microsatellite instability (MSI), chemokine and their receptors were analyzed using TCGA, ESTIMATE algorithm, and TISIDB database...
November 27, 2022: Aging
Eoin P Flanagan, Michael D Geschwind, A Sebastian Lopez-Chiriboga, Kyle M Blackburn, Sanchit Turaga, Sophie Binks, Jennifer Zitser, Jeffrey M Gelfand, Gregory S Day, S Richard Dunham, Stefanie J Rodenbeck, Stacey L Clardy, Andrew J Solomon, Sean J Pittock, Andrew McKeon, Divyanshu Dubey, Anastasia Zekeridou, Michel Toledano, Lindsey E Turner, Steven Vernino, Sarosh R Irani
IMPORTANCE: Autoimmune encephalitis misdiagnosis can lead to harm. OBJECTIVE: To determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4)...
November 28, 2022: JAMA Neurology
Abhishek Tripathi, Kira MacDougall, Guru P Sonpavde
Platinum-based chemotherapy has long been the backbone of treatment for urothelial carcinoma. Immune checkpoint inhibitors have revolutionized the treatment paradigm and significantly improved outcomes for many patients. More recently, targeted agents such as erdafitinib and antibody drug conjugates enfortumab vedotin and sacituzumab govitecan have demonstrated robust efficacy after progression on prior chemotherapy and immunotherapy. Many additional agents are currently under investigation in ongoing clinical trials...
November 28, 2022: Drugs
Joseph Ho, Constance Fiocco, Kristen Spencer
Biliary tract cancers (BTCs) are rare and aggressive tumors that typically present at an advanced stage when surgical resection is no longer considered a therapeutic option. While gemcitabine and cisplatin have been the mainstay of treatment, unique chemotherapy combination strategies, targeted therapies, and immunotherapies have had some clinical efficacy and remain promising areas for clinical research. The use of molecular profiling of BTCs has facilitated the development and subsequent clinical application of novel targeted therapy compounds...
November 28, 2022: Drugs
Jyoti Malhotra, Edward S Kim
PURPOSE OF REVIEW: Oncolytic viruses (OVs) exert their antitumor effect through selective killing of cancer cells and induction of host anti-tumor immunity. This review aims to summarize the recent and current trials with OVs for the treatment of lung cancer. RECENT FINDINGS: Several OVs have been developed for the treatment of lung cancer including adenovirus, coxsackievirus B3, reovirus, and vaccinia virus and trials have demonstrated a safe toxicity profile. Early-phase trials in lung cancer with OVs have reported antiviral immune responses and evidence of clinical benefit...
November 28, 2022: Current Oncology Reports
A Goretzki, J Zimmermann, H Rainer, Y-J Lin, Stefan Schülke
PURPOSE OF REVIEW: Recent high-level publications have shown an intricate connection between immune effector function and the metabolic state of the respective cells. In the last years, studies have begun analyzing the metabolic changes associated with allergies. As the first part of a two-article series, this review will briefly summarize the basics of immune metabolism and then focus on the recently published studies on metabolic changes observed in allergic patients. RECENT FINDINGS: In the last 3 years, immune-metabolic research in allergology had a clear focus on asthma with some studies also reporting findings in food allergy and atopic dermatitis...
November 28, 2022: Current Allergy and Asthma Reports
Daisuke Tomizawa
Acute lymphoblastic leukemia (ALL) in infants accounts for less than 5% of pediatric ALL and is biologically and clinically unique. Approximately 70% to 80% of cases present as an aggressive leukemia with KMT2A gene rearrangement (KMT2A-r), which is one of the most difficult-to-cure forms of pediatric leukemia. Owing to continuing global efforts through multicenter clinical trials since the mid-1990s, a standard of care for infant KMT2A-r ALL, including minimal residual disease-based risk stratifications, "hybrid chemotherapy" incorporating myeloid leukemia-like drugs (e...
November 28, 2022: International Journal of Hematology
Yuta Takeuchi, Seiichiro Inoue, Akio Odaka
BACKGROUND: Immunotherapy may improve the poor prognosis of high-risk neuroblastoma. Programmed cell death-1 (PD-1) is expressed in several cancers. The tyrosine hydroxylase MYCN (TH-MYCN) transgenic mouse model is widely used in neuroblastoma research, but detailed information on its immunological background is lacking. Therefore, we studied the immunological tumor microenvironment and tumor cell surface antigen expression in homozygote and hemizygote mice and effects of antibody therapy against PD-1...
November 28, 2022: Pediatric Surgery International
Alexandre Poirier, Michel L Tremblay
Dendritic cells have been at the forefront of cancer-immunotherapy research for over 2 decades. They elicited that attention by having an unprecedented capacity to mount T cells responses against tumors. However, the clinical use of DC-based vaccination against established malignancies has resulted in limited clinical benefits. Several factors are responsible for limiting the efficacy of DC-based immunotherapy, such as the harmful influence of the tumor microenvironment on DCs activity. New insights into the inner process of DC-mediated T cell activation have supported the development of new strategies that potentiate DCs-based therapies...
November 28, 2022: Cancer Immunology, Immunotherapy: CII
Xiaomi Li, Xiaoyan Ding, Wei Li, Jinglong Chen
BACKGROUND: Currently, there are a few treatment options for unresectable hepatocellular carcinoma (HCC) after progression following sorafenib (SOR) therapy, but with limited benefit. The purpose of this study was to investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with immune checkpoint inhibitors (ICIs) as second-line treatment. METHODS: From May 2018 to May 2021, a total of 93 HCCs who failed SOR treatment were included in this study and divided into TKI group (n = 37) and TKI-ICI group (n = 56)...
November 28, 2022: Cancer Immunology, Immunotherapy: CII
Dandan Zhu, Yuansheng Hu, Zhiwei Jiang, Tuantuan Yang, Kai Chu, Hengming Zhang, Jialei Hu, Xing Meng, Zhijun Tan, Jingliang Wu, Xiaojuan Lian, Changgui Li, Hongxing Pan
Previous phase I to III clinical trials have shown that the inactivated SARS-CoV-2 vaccine namely CoronaVac has good efficacy, safety, and immunogenicity. This phase IV trial aims to evaluate the lot-to-lot consistency, immunogenicity, and safety on a commercial scale in healthy adults, which could provide data to support stable manufacturing. In this single-center, randomized, double-blind study, 1,080 healthy adults aged 26-45 years were randomly assigned into three groups to receive one of three lots of vaccines...
November 28, 2022: Human Vaccines & Immunotherapeutics
Andrew J Pollard, Noni E MacDonald, Eve Dubé, Ken Lamden, Professor David Baxter, Debbie Suggitt, Helen Donovan, Yvonne Gibney, Rino Rappouli, C Wright, E Rodgers, C Trotter, J M Stuartc, N Blake, L Glennie, Jay Lucidarme, Xilian Bai, Aiswarya Lekshmi, Laura Willerton, Stephen A Clark, Ray Borrow
No abstract text is available yet for this article.
November 28, 2022: Human Vaccines & Immunotherapeutics
Jordi Remon, Lizza E L Hendriks, Giannis Mountzios, Rosario García-Campelo, Stephanie P L Saw, Dipesh Uprety, Gonzalo Recondo, Guillermo Villacampa, Martin Reck
Targeted therapies have revolutionized the treatment and improved the outcome for oncogene-driven NSCLC and an increasing number of oncogenic driver therapies have become available. For MET-dysregulated NSCLC (especially MET exon 14 skipping mutations and MET-amplifications, which is one of the most common bypass mechanisms of resistance in oncogene-addicted NSCLC), several anti-MET-targeted therapies have been approved recently (MET exon 14 skipping mutation) and multiple others are in development. In this narrative review, we summarize the role of MET as an oncogenic driver in NSCLC, discuss the different testing methods for exon 14 skipping mutations, gene amplification, and protein overexpression, and review the existing data and ongoing clinical trials regarding targeted therapies in MET-altered NSCLC...
October 29, 2022: Journal of Thoracic Oncology
Laura M Sly, Derek M McKay
As an essential component of immunity, macrophages have key roles in mammalian host defense, tissue homeostasis, and repair, as well as in disease pathogenesis and pathophysiology. A source of fascination and extensive research, in this Opinion we challenge the utility of the M1-M2 paradigm, and discuss the importance of accurate characterization of human macrophages. We comment on the application of single cell analytics to define macrophage subpopulations and how this could advance therapeutic options. We argue that human macrophage cell therapy can be used to alleviate many diseases, and offer a viewpoint on the knowledge gaps that must be filled to render such a therapeutic approach a reality and, ideally, a common future practice in precision medicine...
December 2022: Trends in Immunology
Evan E Gross, Mingjia Li, Ming Yin, Delaney Orcutt, Duncan Hussey, Elliot Trott, Sarah K Holt, Erin R Dwyer, Joel Kramer, Kaylee Oliva, John L Gore, George R Schade, Daniel W Lin, Scott S Tykodi, Evan T Hall, John A Thompson, Anish Parikh, Yuanquan Yang, Katharine A Collier, Abdul Miah, Sherry Mori-Vogt, Megan Hinkley, Amir Mortazavi, Paul Monk, Edmund Folefac, Steven K Clinton, Sarah P Psutka
BACKGROUND: Cytoreductive nephrectomy (CN) for the treatment of metastatic renal cell carcinoma (mRCC) was called into question following the publication of the CARMENA trial. While previous retrospective studies have supported CN alongside targeted therapies, there is minimal research establishing its role in conjunction with immune checkpoint inhibitor (ICI) therapy. OBJECTIVE: To evaluate the association between CN and oncological outcomes in patients with mRCC treated with immunotherapy...
January 2023: Urologic Oncology
Li-Li Huang, Tao-Hsin Tung, Yan-Hong Jiang, Wei-Wei Hu, Yu-Pei Yang
The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis...
November 28, 2022: Human Vaccines & Immunotherapeutics
Qinran Zhang, Suoqin Jin, Xiufen Zou
Although single-cell sequencing has provided a powerful tool to deconvolute cellular heterogeneity of diseases like cancer, extrapolating clinical significance or identifying clinically-relevant cells remains challenging. Here, we propose a novel computational method scAB, which integrates single-cell genomics data with clinically annotated bulk sequencing data via a knowledge- and graph-guided matrix factorization model. Once combined, scAB provides a coarse- and fine-grain multiresolution perspective of phenotype-associated cell states and prognostic signatures previously not visible by single-cell genomics...
November 28, 2022: Nucleic Acids Research
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