tbuckley/cabot-search huggingface dataset:
A Versatile Chitosan‐Based Hydrogel Accelerates Infected Wound Healing via Bacterial Elimination, Antioxidation, Immunoregulation, and Angiogenesis (Adv. Healthcare Mater. 19/2024)
Authors: Ye Zhang, Sinan Chen, Xian Qin, Ai Guo, Kai Li, Lixue Chen, Weiwei Yi, Zhongliang Deng, Franklin R. Tay, Wenbo Geng, Li Miao, Yang Jiao, Bailong Tao
Journal: Advanced Healthcare Materials (2024)
Highly Potent Cationic Chitosan Derivatives Coupled to Antimicrobial Peptide Dendrimers to Combat <i>Pseudomonas aeruginosa</i> (Adv. Healthcare Mater. 19/2024)
Authors: Olivier Jordan, Bee Ha Gan, Sari Alwan, Karl Perron, Emmanuelle Sublet, Verena Ducret, Hua Ye, Gerrit Borchard, Jean‐Louis Reymond, Viorica Patrulea
Journal: Advanced Healthcare Materials (2024)
TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment
Authors: Fadi Azar, Jules Deforges, Christelle Demeusoit, Patricia Kleinpeter, Christelle Remy, Nathalie Silvestre, Johann Foloppe, Laetitia Fend, Clémentine Spring-Giusti, Eric Quéméneur, Jean-Baptiste Marchand
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background TG6050 was designed as an improved oncolytic vector, combining the intrinsic properties of vaccinia virus to selectively replicate in tumors with the tumor-restricted expression of recombinant immune effectors to modify the tumor immune phenotype. These properties might be of particular interest for “cold” tumors, either poorly infiltrated or infiltrated with anergic T cells. Methods TG6050, an oncolytic vaccinia virus encodes single-chain human interleukin-12 (hIL-12) and full-length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. The relevant properties of TG6050 (replication, cytopathy, transgenes expression and functionality) were extensively characterized in vitro . The biodistribution and pharmacokinetics of the viral vector, @CTLA-4 and IL-12, as well as antitumoral activities (alone or combined with immune checkpoint inhibitors) were investigated in several “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. The mechanism of action was deciphered by monitoring both systemic and intratumoral immune responses, and by tumor transcriptome analysis. The safety of TG6050 after repeated intravenous administrations was evaluated in cynomolgus monkeys, with a focus on the level of circulating IL-12. Results Multiplication and propagation of TG6050 in tumor cells in vitro and in vivo were associated with local expression of functional IL-12 and @CTLA-4. This dual mechanism translated into a strong antitumoral activity in both “cold” and “hot” tumor models (B16F10, LLC1 or EMT6, CT26, respectively) that was further amplified when combined with anti-programmed cell death protein-1. Analysis of changes in the tumor microenvironment (TME) after treatment with TG6050 showed increases in interferon-gamma, of CD8+T cells, and of M1/M2 macrophages ratio, as well as a drastic decrease of regulatory T cells. These local modifications were observed alongside bolstering a systemic and specific antitumor adaptive immune response. In toxicology studies, TG6050 did not display any observable adverse effects in cynomolgus monkeys. Conclusions TG6050 effectively delivers functional IL-12 and @CTLA-4 into the tumor, resulting in strong antitumor activity. The shift towards an inflamed TME correlated with a boost in systemic antitumor T cells. The solid preclinical data and favorable benefit/risk ratio paved the way for the clinical evaluation of TG6050 in metastatic non-small cell lung cancer ( NCT05788926 trial in progress).
ImmunoPET imaging of LAG-3 expression in tumor microenvironment with<sup>68</sup>Ga-labelled cyclic peptides tracers: from bench to bedside
Authors: Ming Zhou, Bei Chen, Chenxi Lu, Jinhui Yang, Peng Liu, Xiaobo Wang, Shuo Hu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Lymphocyte activation gene 3 (LAG-3) has been considered as the next generation of immune checkpoint and a promising prognostic biomarker of immunotherapy. As with programmed cell death protein-1/programmed death-ligand 1 and cytotoxic T-lymphocyte antigen-4 inhibitors, positron emission tomography (PET) imaging strategies could benefit the development of clinical decision-making of LAG-3-related therapy. In this study, we developed and validated 68 Ga-labeled cyclic peptides tracers for PET imaging of LAG-3 expression in bench-to-bedside studies. Methods A series of LAG-3-targeted cyclic peptides were modified and radiolabeled with 68 GaCl 3 and evaluated their affinity and specificity, biodistribution, pharmacokinetics, and radiation dosimetry in vitro and in vivo. Furthermore, hu-PBL-SCID (PBL) mice models were constructed to validate the capacity of [ 68 Ga]Ga-CC09-1 for mapping of LAG-3 + lymphocytes infiltrates using longitudinal PET imaging. Lastly, [ 68 Ga]Ga-CC09-1 was translated into the first-in-human studies to assess its safety, biodistribution and potential for imaging of LAG-3 expression. Results A series of cyclic peptides targeting LAG-3 were employed as lead compounds to design and develop 68 Ga-labeled PET tracers. In vitro binding assays showed higher affinity and specificity of [ 68 Ga]Ga-CC09-1 in Chinese hamster ovary-human LAG-3 cells and peripheral blood mononuclear cells. In vivo PET imaging demonstrated better imaging capacity of [ 68 Ga]Ga-CC09-1 with a higher tumor uptake of 1.35±0.33 per cent injected dose per gram and tumor-to-muscle ratio of 17.18±3.20 at 60 min post-injection. Furthermore, [ 68 Ga]Ga-CC09-1 could detect the LAG-3 + lymphocyte infiltrates in spleen, lung and salivary gland of PBL mice. In patients with melanoma and non-small cell lung cancer, primary lesions with modest tumor uptake were observed in [ 68 Ga]Ga-CC09-1 PET, as compared with that of [ 18 F]FDG PET. More importantly, [ 68 Ga]Ga-CC09-1 delineated the heterogeneity of LAG-3 expression within large tumors. Conclusion These findings consolidated that [ 68 Ga]Ga-CC09-1 is a promising PET tracer for quantifying the LAG-3 expression in tumor microenvironment, indicating its potential as a companion diagnostic for patients stratification and therapeutic response monitoring in anti-LAG-3 therapy.
Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214
Authors: Charlene M Mantia, Opeyemi A Jegede, Elizabeth R Plimack, Thomas Powles, Robert J Motzer, Nizar M Tannir, Chung-Han Lee, Yoshihiko Tomita, Martin H Voss, Toni K Choueiri, Brian I Rini, Hans J Hammers, Bernard Escudier, Laurence Albigès, Lisa Rosenblatt, Michael B Atkins, Meredith M Regan, David F McDermott
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures. Methods Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method. Results At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs. Conclusions Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN. Trial registration number NCT02231749 .
Impact of smoking on cost‐effectiveness of 10–48 years of periodontal care
Authors: Andrea Ravidà, Muhammad H. A. Saleh, Iya H. Ghassib, Musa Qazi, Purnima S. Kumar, Hom‐Lay Wang, Paul I. Eke, Wenche S. Borgnakke
Journal: Periodontology 2000 (2024)

The study aims were (1) to explore whether "periodontal treatment" consisting of surgical therapy (flap, resective, or regenerative) or scaling and root planing treatment with long-term periodontal maintenance treatment, is cost-effective in terms of preventing periodontitis-attributable tooth extraction and replacement by implant-supported crowns ("extraction/replacement"); (2) to assess the effect of cigarette smoking on this cost-effectiveness. Data for this observational retrospective study were collected from dental charts of patients who had received periodontal therapy and at least annual follow-up visits for >10 years were analyzed by linear regression generalized estimating equations and generalized linear models. Among 399 adults (199 males, 200 females), those with the least mean annual treatment cost experienced the greatest mean annual costs for extraction/replacement, indicating general cost-effectiveness. Cigarette smoking adversely impacted this cost-effectiveness, with current heavy smokers experiencing no cost-effectiveness. Former smokers with Grade C periodontitis benefitted most, whereas smoking did not influence cost-effectiveness for Grade B periodontitis. Assessed by mean annual costs of "extraction/replacement," periodontal treatment was cost-effective, which decreased in a dose-response manner by former and current smoking intensity. Cigarette smoking should be factored into treatment planning and cost-effective analyses of periodontal treatment. Smoking cessation should be encouraged.
<scp>CD4</scp><sup>+</sup><scp>CD8α<sup>low</sup></scp> T Cell Clonal Expansion Dependent on Costimulation in Patients With Rheumatoid Arthritis
Authors: Felix Beck, Phuong Nguyen, Anne Hoffmann, Lucie Loyal, Andreas Thiel, Marc Melzer, Hannah Apel, Matthias Pierer, Marco Krasselt, Olga Seifert, Anne‐Marie Glimm, Tobias Hagemann, Kathrin Rothe, Ulf Wagner
Journal: Arthritis & Rheumatology (2024)

Objective CD4 + CD8 + T cells are increased in patients with rheumatoid arthritis (RA). They are not only associated with joint erosions in established disease but are also present in the preclinical stages of RA. This study aims to further investigate their expansion in the context of T cell clonality in patients with RA, as well as their responsiveness to T cell–targeted treatment. Methods Single‐cell RNA (scRNA) and single‐cell T cell receptor (TCR) sequencing data were used to determine coreceptor expression and TCR sequences to assess the clonality of CD4 + CD8 + T cells in patients with RA (n = 3) and healthy controls (n = 2). Peripheral CD4 + CD8 + T cells and their subpopulations were measured in patients with RA (n = 53), patients with psoriatic arthritis (PsA; n = 52), and healthy donors (n = 50) using flow cytometry. In addition, changes in CD4 + CD8 + T cell frequency were prospectively observed in patients with RA receiving therapy with abatacept for 12 weeks. Results We observed an increase of CD4 + T cells expressing CD8α in patients with RA, both in comparison to patients with PsA and healthy controls. Clonality analysis revealed that these CD4 + CD8α low T cells are part of large T cell clones, which cluster separately from CD4 + CD8 − T cell clones in the scRNA sequencing (scRNA‐seq) gene expression analysis. Treatment with abatacept significantly reduced the frequency of peripheral CD4 + CD8α low T cells, and this was linked to reduction in disease activity. Conclusion In patients with RA, clonal expansion of CD4 + T cell culminates in the emergence of peripheral CD4 + CD8α low T cells, which are associated with disease activity and diminished upon abatacept treatment and could contribute to disease pathogenesis. image
Extracellular Vesicle‐Inspired Minimalist Flexible Nanocapsules Assembled with Whole Active Ingredients for Highly Efficient Enhancement of DC‐Mediated Tumor Immunotherapy
Authors: Ao He, Qiang Li, Meng Dang, Wei Lu, Xiaoye Li, Zhuo Dai, Meng Ding, Yu Zhang, Heng Dong, Zhaogang Teng, Yongbin Mou
Journal: Advanced Healthcare Materials (2024)

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8
FXa-mediated PAR-2 promotes the efficacy of immunotherapy for hepatocellular carcinoma through immune escape and anoikis resistance by inducing PD-L1 transcription
Authors: Xuemei Li, Lei Gao, Bofang Wang, Jike Hu, Yang Yu, Baohong Gu, Lin Xiang, Xiaomei Li, Haiyuan Li, Tao Zhang, Yunpeng Wang, Chenhui Ma, Jiahong Dong, Jianrong Lu, Alexandra Lucas, Hao Chen
Journal: Journal for ImmunoTherapy of Cancer (2024)

The high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC.
Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy
Authors: Haider Al-janabi, Katy Moyes, Richard Allen, Matthew Fisher, Mateus Crespo, Bora Gurel, Pasquale Rescigno, Johann de Bono, Harry Nunns, Christopher Bailey, Anna Junker-Jensen, Munitta Muthana, Wayne A Phillips, Helen B Pearson, Mary-Ellen Taplin, Janet E Brown, Claire E Lewis
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNβ), would stimulate antitumor immunity and delay CRPC. Methods We used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2′3′-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT. Results TAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-β), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-β selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNβ. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs. Conclusion Together, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer.
Preclinical activity of allogeneic SLAMF7-specific CAR T-cells (UCARTCS1) in multiple myeloma
Authors: Charlotte L B M Korst, Chloe O’Neill, Wassilis S C Bruins, Meliha Cosovic, Inoka Twickler, Christie P M Verkleij, Diane Le Clerre, Maria Themeli, Isabelle Chion-Sotinel, Sonja Zweegman, Roman Galetto, Tuna Mutis, Niels W C J van de Donk
Journal: Journal for ImmunoTherapy of Cancer (2024)

Autologous BCMA-specific CAR T-cell therapies have substantial activity in multiple myeloma (MM). However, due to logistical limitations and BCMA
TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD
Authors: Baokai Sun, Xiaoqian Ding, Jie Tan, Jie Zhang, Xueru Chu, Shuimi Zhang, Shousheng Liu, Zhenzhen Zhao, Shiying Xuan, Yongning Xin, Likun Zhuang
Journal: Clinical and Molecular Hepatology (2024)

Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
An Immunomodulator‐Boosted Lactococcus Lactis Platform For Enhanced In Situ Tumor Vaccine
Authors: Mengna Sun, Tianyu Shi, Subiyinuer Tuerhong, Mengru Li, Qiaoli Wang, Changchang Lu, Lu Zou, Qinghua Zheng, Yingxin Wang, Juan Du, Rutian Li, Baorui Liu, Fanyan Meng
Journal: Advanced Healthcare Materials (2024)

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.
CKD Risk Stratification
Authors: Fouad T. Chebib, Neera K. Dahl
Journal: Journal of the American Society of Nephrology (2024)

1Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida 2Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota Correspondence: Dr. Neera K. Dahl, email: [email protected] See related article, "Kidney Volume and Risk of Incident Kidney Outcomes," on pages XXX–XXX.
NMR-based analysis of impact of siRNA mixing conditions on internal structure of siRNA-loaded LNP
Authors: Keisuke Ueda, Yui Sakagawa, Tomoki Saito, Fumie Sakuma, Hiroki Tanaka, Hidetaka Akita, Kenjirou Higashi, Kunikazu Moribe
Journal: Journal of Controlled Release (2024)

This study aimed to assess the applicability of solution-state
Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder: a benign or malignant process?
Authors: Rein Willemze
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder: a benign or malignant process? Get access Rein Willemze Rein Willemze Writing - original draft, Writing - review & editing Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands Email: rein.willemze@planet.nl https://orcid.org/0000-0002-4561-7616 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae303, https://doi.org/10.1093/bjd/ljae303 Published: 26 July 2024 Article history Received: 12 July 2024 Accepted: 12 July 2024 Published: 26 July 2024 Corrected and typeset: 21 August 2024
Inhibition of endothelial-to-mesenchymal transition in a large animal preclinical arteriovenous fistula model leads to improved remodelling and reduced stenosis
Authors: Yang Xu, Adam Korayem, Ana S Cruz-Solbes, Nirupama Chandel, Tomoki Sakata, Renata Mazurek, Spyros A Mavropoulos, Taro Kariya, Tadao Aikawa, Kelly P Yamada, Valentina D'Escamard, Bhargavi V'Gangula, Andrew H Baker, Lijiang Ma, Johan L M Björkegren, Valentin Fuster, Manfred Boehm, Kenneth M Fish, Rami Tadros, Kiyotake Ishikawa, Jason C Kovacic
Journal: Cardiovascular Research (2024)

Vein grafts are used for many indications, including bypass graft surgery and arterio-venous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia and adverse remodeling. Recently, endothelial to mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts. We aimed to evaluate the clinical potential of inhibiting EndMT, and developed the first dedicated preclinical model to study the efficacy of local EndMT inhibition immediately prior to AVF creation.