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JOURNAL ARTICLE
Yujuan Dong, Jiaxun Jade Liu, Yunfei Zhou, Wei Kang, Shanglin Li, Alvin Hk Cheung, Hu Yi, Rui Liao, Nathalie Wong, Chi Chun Wong, Simon Ng, Jun Yu
Immunoglobulin VSTM2A is a top-ranked secretory protein that frequently silenced during colorectal carcinogenesis, however, its role in immune modulation remains largely unknown. Bioinformatic and immunohistochemistry analysis of human colorectal specimens and Vstm2a+/- knockout mice indicated that VSTM2A positively correlated with CD8a and immune infiltration in both physiological and pathological conditions. We then utilized liquid chromatography-mass spectrometry to pinpoint PD-L1 as a membrane receptor of VSTM2A...
September 17, 2024: Molecular Therapy
#22
JOURNAL ARTICLE
David W Scott
No abstract text is available yet for this article.
September 15, 2024: Molecular Therapy
#23
JOURNAL ARTICLE
Leila Amini, Lena Peter, Michael Schmueck-Henneresse
No abstract text is available yet for this article.
September 11, 2024: Molecular Therapy
#24
JOURNAL ARTICLE
Jui-Sheng Wu, Helike Lõhelaid, Chih-Chin Shih, Hock-Kean Liew, Vicki Wang, Wei-Fen Hu, Yuan-Hao Chen, Mart Saarma, Mikko Airavaara, Kuan-Yin Tseng
Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation...
September 9, 2024: Molecular Therapy
#25
JOURNAL ARTICLE
Brian C Gilger, Tomoko Hasegawa, R Bryan Sutton, Jacquelyn J Bower, Chengwen Li, Matthew L Hirsch
Corneal blindness affects greater than 5 million individuals, with over 180,000 corneal transplantations (CTs) performed annually. Inhigh-risk CTs, almost all grafts are rejected within 10 years. Herein, adeno-associated virus (AAV) ex vivo gene therapy was investigated to establish immune tolerance in the corneal allograft to prevent high-risk CT rejection. Our previous work has demonstrated that HLA-G contributes to ocular immune privilege by inhibiting both immune cells and neovascularization; however, homodimerization is a rate-limiting step for optimal HLA-G function...
September 7, 2024: Molecular Therapy
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JOURNAL ARTICLE
Shengxi Shen, Ping Wang, Pei Wu, Pengyu Huang, Tian Chi, Wenqing Xu, Ying Xi
Wnt/β-catenin signaling is an attractive target for regenerative medicine. A powerful driver of stem cell activity and hence tissue regeneration, Wnt signaling can promote fibroblast proliferation and activation, leading to fibrosis, while prolonged Wnt signaling is potentially carcinogenic. Thus, to harness its therapeutic potential, the activation of Wnt signaling must be transient, reversible and tissue-specific. In the lung, Wnt signaling is essential for alveolar stem cell activity and alveolar regeneration, which is impaired in lung fibrosis...
September 7, 2024: Molecular Therapy
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JOURNAL ARTICLE
Xin Wei, Linlin Zhao, Fang Yang, Yajing Yang, Huixiang Zhang, Kaixin Du, Xinxin Tian, Ruihua Fan, Guangxu Si, Kailun Wang, Yulu Li, Zhizhong Wei, Miaomiao He, Jianhua Sui
Intratumoral regulatory T cells (Tregs) express high levels of CD25 and TIGIT, which are also recognized as markers of effector T cell (Teff) activation. Targeting these molecules each alone with monoclonal antibodies (mAbs) poses a risk of concurrently depleting both Teffs and peripheral Tregs, thereby compromising the effectiveness and selectivity of intratumoral Treg depletion. Here, leveraging the increased abundance of CD25+ TIGIT+ double positive Tregs in the solid tumor microenvironment (but not in peripheral tissues), we explored the feasibility of using a CD25×TIGIT bispecific antibody (bsAb) to selectively deplete intratumoral Tregs...
September 7, 2024: Molecular Therapy
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JOURNAL ARTICLE
Jenell Volkov, Daniel Nunez, Tahseen Mozaffar, Jason Stadanlick, Mallorie Werner, Zachary Vorndran, Alexandra Ellis, Jazmean Williams, Justin Cicarelli, Quynh Lam, Thomas Furmanak, Chris Schmitt, Fatemeh Hadi-Nezhad, Daniel Thompson, Claire Miller, Courtney Little, David Chang, Samik Basu
Under compassionate use, chimeric antigen receptor (CAR) T-cells have elicited durable remissions in patients with refractory idiopathic inflammatory myopathies (IIM)1 . Here, we report on the safety, efficacy, and correlative data of the first subject with the immune-mediated necrotizing myopathy (IMNM) subtype of IIM who received a fully human, 4-1BBz anti-CD19-CAR T-cell therapy (CABA-201) in the RESET-Myositis™ phase I/II trial (NCT06154252). CABA-201 was well-tolerated following infusion. Notably, no evidence of cytokine release syndrome (CRS) or immune effector-cell associated neurotoxicity syndrome (ICANS) was observed...
September 7, 2024: Molecular Therapy
#29
JOURNAL ARTICLE
Liping Zhao, Chuo Li, Shiyu Zuo, Yajing Han, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Ying Yuan, Zhenglong Tian, Kaiting Tang, Yibing Zhang, Qing Niu, Jiecheng Zhang, Alex H Chang, Yuechen Luo, Xiaoming Feng, Jing Pan
Chimeric antigen receptor (CAR) T-cell therapy showed preliminary activity in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL). However, many obstacles remain, including manufacturing difficulties and risk of infections. This phase I study (NCT04840875) evaluated autologous CD7 CAR T cells manufactured without pre-selection of healthy T cells in r/r T-ALL. Thirty patients (29 children and one adult) with a median of two lines of prior therapy but without detectable peripheral leukemia were enrolled...
September 6, 2024: Molecular Therapy
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JOURNAL ARTICLE
Cristiano Fieni, Stefania Livia Ciummo, Carlo Sorrentino, Simona Marchetti, Simone Vespa, Paola Lanuti, Lavinia Vittoria Lotti, Emma Di Carlo
Prostate-cancer (PC) is a leading cause of cancer-related deaths in men worldwide. Interleukin-(IL)-30 is a PC-progression driver, and its suppression would be strategic for fighting metastatic disease. Biocompatible Lipid-Nanoparticles (NPs) were loaded with CRISPR/Cas9gRNA to delete human(h)IL30-gene and functionalized with anti-PSCA-Abs (Cas9hIL30-PSCA-NPs). Efficiency of the NPs in targeting IL30 and metastatic potential of PC cells was examined in vivo, in xenograft models of lung metastasis, and in vitro, by using 2-Organ-on-Chip (2-OC), containing 3D-spheroids of IL30+ PC-Endothelial-Cell(EC) co-cultures in circuit with either Lung-mimicking-spheroids, or Bone-marrow(BM)-niche-mimicking-scaffolds...
September 6, 2024: Molecular Therapy
#31
JOURNAL ARTICLE
Fanglin Gong, Bowen Li
No abstract text is available yet for this article.
September 4, 2024: Molecular Therapy
#32
REVIEW
Yiwei Hu, Yunzeng Zou, Liang Qiao, Ling Lin
Cardiomyopathy is a prevalent cardiovascular disease that affects individuals of all ages and can lead to life-threatening heart failure. Despite its variety in types, each with distinct characteristics and causes, our understanding of cardiomyopathy at a systematic biology level remains incomplete. Mass spectrometry-based techniques have emerged as powerful tools, providing a comprehensive view of the molecular landscape and aiding in the discovery of biomarkers and elucidation of mechanism. This review highlights the significant potential of integrating proteomic and metabolomic approaches with specialized databases to identify biomarkers and therapeutic targets across different types of cardiomyopathies...
September 3, 2024: Molecular Therapy
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JOURNAL ARTICLE
Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding.
Na Li, Nanxin Gong, Baoxin Duan, Yongyan Zhang, Yi Jian, Yanqin Xu, Jinming Liu, Xiaoqian Wang, Xiaoqi Zhang, Mingjuan Du, Feilong Zhou, Jiliang Zhao, Xiangchen Guan, Xiangda Peng, Sheng Wang, Hongkai Zhang, Xin Li
Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb...
September 2, 2024: Molecular Therapy
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JOURNAL ARTICLE
Iqra Ajmal, Muhammad Asad Farooq, Yixin Duan, Jie Yao, Yaoxin Gao, Xinhui Hui, Yujia Ge, Yiran Chen, Yaojun Ren, Bingtan Du, Wenzheng Jiang
Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in patients with solid tumors. Recent in vitro and in vivo data have shown that adrenoceptor beta-2 (ADRB2) is a novel checkpoint receptor that inhibits T cell-mediated anti-tumor responses. To inhibit ADRB2-mediated inhibitory signaling, we downregulated ADRB2 in CAR-T (shβ2 -CAR-T) cells via RNA interference, assessed different parameters, and compared them with conventional second-generation CAR-T cells. ADRB2 knockdown CAR-T cells exhibited enhanced cytotoxicity against prostate cancer cell lines in vitro, by increasing CD69, CD107a, GzmB, IFN-γ, T-bet, and GLUT-1...
September 2, 2024: Molecular Therapy
#35
JOURNAL ARTICLE
Zhuo-Kun Chen, Shuo Zheng, Yan Long, Kui-Ming Wang, Bo-Lin Xiao, Jin-Bang Li, Wei Zhang, Heng Song, Gang Chen
Programmed death-ligand 1 (PD-L1) on tumor-derived small extracellular vesicles (sEVs) limits therapeutic effectiveness by interacting with the PD-1 receptor on host immune cells. Targeting the secretion of sEV PD-L1 has emerged as a promising strategy to enhance immunotherapy. However, the lack of small-molecule inhibitors poses a challenge for clinical translation. In this study, we developed a target and phenotype dual-driven high-throughput screening (TAP-HTS) strategy that combined virtual screening with nanoflow-based experimental verification...
August 31, 2024: Molecular Therapy
#36
JOURNAL ARTICLE
Hong-Qing Zhang, Ya-Nan Zhang, Cheng-Lin Deng, Qin-Xuan Zhu, Zhe-Rui Zhang, Xiao-Dan Li, Zhi-Ming Yuan, Bo Zhang
As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins, have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of Ebola virus-like vesicles (eVLVs) incorporating both EBOV GP and VP40...
August 31, 2024: Molecular Therapy
#37
Hossein A Hamed, Adly Yacoub, Margaret A Park, Patrick J Eulitt, Rupesh Dash, Devanand Sarkar, Igor P Dmitriev, Maciej S Lesniak, Khalid Shah, Steven Grant, David T Curiel, Paul B Fisher, Paul Dent
No abstract text is available yet for this article.
August 29, 2024: Molecular Therapy
#38
JOURNAL ARTICLE
João Fonseca-Gomes, Tiago Costa-Coelho, Mafalda Ferreira-Manso, Sara Inteiro-Oliveira, Sandra H Vaz, Nuno Alemãn-Serrano, Henrique Atalaia-Barbacena, Leonor Ribeiro-Rodrigues, Rita M Ramalho, Rui Pinto, Hugo Vicente Miranda, Sara R Tanqueiro, Carolina de Almeida-Borlido, Maria João Ramalho, Catarina Miranda-Lourenço, Rita F Belo, Catarina B Ferreira, Vera Neves, Diogo M Rombo, Ricardo Viais, Ivo C Martins, André Jerónimo-Santos, António Caetano, Nuno Manso, Petra Mäkinen, Mikael Marttinen, Mari Takalo, Michael Bremang, Ian Pike, Annakaisa Haapasalo, Joana A Loureiro, Maria Carmo Pereira, Nuno C Santos, Tiago F Outeiro, Miguel A R B Castanho, Adelaide Fernandes, Mikko Hiltunen, Carlos B Duarte, Eero Castrén, Alexandre de Mendonça, Ana M Sebastião, Tiago M Rodrigues, Maria José Diógenes
In Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs Brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, as well as synaptic transmission and plasticity. Using cerebrospinal fluid and post-mortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage...
August 27, 2024: Molecular Therapy
#39
JOURNAL ARTICLE
Hector Ribeiro Benatti, Vania Anagnostakou, Toloo Taghian, Erin F Hall, Sarah Nath, Carl B Heilman, Brandon M Beneduce, Anita Leporati, Christopher Raskett, Mark Epshtein, Robert King, Matthew J Gounis, Adel M Malek, Heather L Gray-Edwards
Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution...
August 26, 2024: Molecular Therapy
#40
JOURNAL ARTICLE
Ragan A Pitner, Jaime L Chao, Noelle P Dahl, Meng-Ni Fan, Xiaohe Cai, Nathan G Avery, Kelsey Roe, P Clint Spiegel, Carol H Miao, Michael Y Gerner, Richard G James, David J Rawlings
Antibody inhibitors pose an ongoing challenge to the treatment of subjects with inherited protein deficiency disorders, limiting the efficacy of both protein replacement therapy and corrective gene therapy. Beyond their central role as producers of serum antibody, B cells also exhibit many unique properties that could be exploited in cell therapy applications, notably including antigen-specific recognition and the linked capacity for antigen presentation. Here we employed CRISPR/Cas9 to demonstrate that ex vivo antigen-primed Blimp1-knockout "decoy" B cells, incapable of differentiation into plasma cells, participated in and downregulated host antigen-specific humoral responses after adoptive transfer...
August 26, 2024: Molecular Therapy
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