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| Open AccessT-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
CD3 bispecific antibodies (bsAbs) have demonstrated promising clinical responses in hematological malignancies but clinical benefit in solid tumors has been limited. Here the authors report that pre-treatment vaccination promotes the infiltration of tumor-(un)related effector CD8 T cells, improving the efficacy of CD3 bsAbs in solid tumors.
- Jim Middelburg
- , Marjolein Sluijter
- & Thorbald van Hall
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| Open AccessMetabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines
Extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. Here, the authors report a universal metabolic tagging technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV-based cancer vaccines.
- Rimsha Bhatta
- , Joonsu Han
- & Hua Wang
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| Open AccessImmuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients
Efficacy of dendritic cell (DC)-based vaccines remains unsatisfactory. Here the authors analyse the transcriptomic and immune-metabolic profiles of DCs from patients enrolled in a DC vaccine trial in late-stage melanoma, suggesting that the metabolic profile of DC is associated with the immunostimulatory potential of the cancer vaccine.
- Juraj Adamik
- , Paul V. Munson
- & Lisa H. Butterfield
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| Open AccessBiosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation
Bacteria have been exploited as a potential bio-factory for the synthesis of nanoparticles. Here the authors report the generation of gold nanoparticles from Escherichia coli and show their application for eliciting hyperthermia and anti-tumor immune responses in preclinical cancer models.
- Hao Qin
- , Yang Chen
- & Ruifang Zhao
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| Open AccessEnrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence
Decreased survival after surgery is often associated to post-operative tumor recurrence and metastasis. Here the authors describe a DNA hydrogel enabling monitoring of tumor recurrence and spatiotemporally controlled photodynamic immunotherapy to prevent post-operative tumor recurrence and metastasis.
- Danyu Wang
- , Jingwen Liu
- & Kaixiang Zhang
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| Open AccessNanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy
Targeting the TGF-β signaling pathway has been exploited to relieve immunosuppression in the tumor microenvironment. Here the authors describe the design of a nanoplatform integrating the TGF-β receptor 1 inhibitor LY2157299 and the ROS-responsive JQ1 pro-drug, promoting anti-tumor immune responses in preclinical cancer models.
- Mengxue Zhou
- , Jiaxin Wang
- & Haijun Yu
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Article
| Open AccessImmunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease
Acid sphingomyelinase (ASM) is a sphingolipid metabolizing enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide, and previous work has shown it is upregulated in models of Alzheimer’s disease. Here the authors demonstrate in a mouse model of Alzheimer’s disease that antibody-based immunotherapy targeting plasma ASM resulted in attenuated neuropathological features by suppressing pathogenic Th17 cells.
- Byung Jo Choi
- , Min Hee Park
- & Jae-sung Bae
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| Open AccessAnalysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources
Although COVID-19 convalescent plasma is commonly used for the treatment of immunosuppressed patients, this approach has yielded mixed results. Here, the authors present a systematic review of Omicron-neutralization data in convalescent plasma from vaccinated and unvaccinated individuals.
- David J. Sullivan
- , Massimo Franchini
- & Daniele Focosi
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| Open AccessA phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma
Ad-sig-hMUC1/ecdCD40L is a recombinant adenovirus vaccine comprising human MUC1 antigen fused to the extracellular domain of the CD40 ligand. Here the authors report the result of a phase I clinical trial of Ad-sig-hMUC1/ecdCD40L in patients with advanced adenocarcinoma.
- Tira J. Tan
- , W. X. Gladys Ang
- & Han Chong Toh
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| Open AccessTGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine
TGF-β has been shown to regulate stem-like CD8 + T cell differentiation into tissue resident memory T cells in chronic infection. Here authors show that in tumour-bearing mice, a similar TGF-βdependent CD8 + T cell differentiation program is carried out in the draining lymph nodes, which impedes generation of anti-tumor migratory effector T cells upon future vaccination.
- Guo Li
- , Saranya Srinivasan
- & Nu Zhang
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Article
| Open AccessCAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies
The success rate of chimeric antigen receptor T cell therapy is high in blood cancers, yet individual patient characteristics might reduce therapeutic benefit. Here authors show that therapeutic response in multiple myeloma, acute lymphoblastic leukemia and non-Hodgkin lymphoma, and occurrence of severe cytokine release syndrome in multiple myeloma are associated with specific gut microbiome alterations.
- Yongxian Hu
- , Jingjing Li
- & He Huang
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| Open AccessMultifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade
Radiotherapy can activate an in situ vaccine response and promote response to immune checkpoint inhibitors. Here the authors design a multifunctional nanoparticle to enhance tumor antigen presentation and modulate the tumor immune microenvironment following radiotherapy, showing improved anti-tumor immune responses in radiotherapy-treated tumors when combined with immune checkpoint inhibitors.
- Ying Zhang
- , Raghava N. Sriramaneni
- & Zachary S. Morris
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| Open AccessPromotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
Protection against SARS-CoV-2 infection involves T cell and B cell responses but only studying one or the other has proved difficult. Here the authors immunise with a fusion protein construct of N and RBD proteins from SARS-CoV-2 and find that this promotes protection in animal models preferentially via T cells.
- Julia T. Castro
- , Patrick Azevedo
- & Ricardo T. Gazzinelli
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| Open AccessSpatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy
Several approaches have been recently proposed to engineer bacteria for cancer immunotherapy. Here the authors design an ultrasound-responsive bacterium for the controlled release of IFNy at the tumor site, promoting anti-tumor immune responses in preclinical models.
- Yuhao Chen
- , Meng Du
- & Fei Yan
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| Open AccessBiomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy
Antibodies targeting OX40 or CD137, two T cell costimulatory receptors, have been shown to improve antitumor immunity. Here the authors design a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in vivo, improving efficacy of anti-OX40 and anti-CD137 antibody therapy in preclinical tumor models.
- Wenqing Li
- , Xinfu Zhang
- & Yizhou Dong
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| Open AccessA modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity
Successful cancer immune therapy correlates with a T cell-inflamed tumour microenvironment. Authors show here that co-administration of a self-adjuvanting protein vaccine and an antigen-expressing oncolytic virus in an optimised regimen strongly enhances T cell immunogenicity and may turn non-inflamed tumours proinflammatory and less resistant to checkpoint blockade therapy.
- Krishna Das
- , Elodie Belnoue
- & Guido Wollmann
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| Open AccessFrancisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
Mucosal-Associated Invariant T (MAIT) cells are associated with established functions during bacterial infection. Here the authors show inoculation with Francisella tularensis results in induction of MAIT cells associated with prototypic Th1 immunity and confer protection to systemic and local infection.
- Zhe Zhao
- , Huimeng Wang
- & Zhenjun Chen
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| Open AccessIntegrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.
- Ziad Bakouny
- , David A. Braun
- & Toni K. Choueiri
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| Open AccessEscherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy
TLR4 agonists have been proposed as immunotherapeutics in cancer. Here, the authors show the TLR4-dependent adjuvant effect of FimH, an E. coli adhesin, in promoting dendritic cell mediated-T cell activation and response to immune checkpoint blockade in preclinical cancer models.
- Wei Zhang
- , Li Xu
- & Jun-O Jin
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| Open AccessSynergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies
CD40 agonists have been investigated as a strategy to awaken the immune system against cancers. Here, the authors use a virus encoding CD40L and tumour-associated antigens to enhance innate and adaptive immunity that together with tumour targeting antibodies controls the growth of tumours in mice.
- José Medina-Echeverz
- , Maria Hinterberger
- & Henning Lauterbach
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| Open AccessTissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells
Immunotherapy can induce antigen spreading of antitumor T cell response, which correlates with better outcomes. Here the authors show that tissue-resident memory CD8 T cells promote antigen spreading via lysing tumor cells and promoting their uptake and cross-presentation by dendritic cells, thereby eliciting de novo T cell responses.
- Evelyn Menares
- , Felipe Gálvez-Cancino
- & Alvaro Lladser
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| Open AccessTumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity
The anti-tumour immune response greatly depends on the number of tumour neoantigens. Here the authors show in mouse models that a therapeutic strategy aimed at increasing the number of neoantigens via downregulating TAP, an antigen processing associated protein, enhances anti-tumour immunity and the efficacy of immunotherapy.
- Greta Garrido
- , Brett Schrand
- & Eli Gilboa
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| Open AccessHorse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
Antivenoms, obtained by venom immunization, have narrow species coverage due to low immunogenicity of venom neurotoxins. Here the authors immunize horses with a designed recombinant consensus neurotoxin, and the resulting antisera protect mice from envenomation by a broad spectrum of elapid snakes.
- Guillermo de la Rosa
- , Felipe Olvera
- & Gerardo Corzo
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| Open AccessSkin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8+ effector recruitment to mucosal tissues
Mucosal immunisation is important for initiating mucosal CD8+ Tcell responses but mucosal recruitment of protective CD8+ T cells can also be induced by skin immunisation. Here the authors examine the underlying mechanism and report a novel role for ILC1 recruiting CD8+ T cells to the mucosa after skin immunisation.
- Marija Zaric
- , Pablo D. Becker
- & Linda S. Klavinskis
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| Open AccessModifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2
IL-2 is used systemically for cancer therapy but it is associated with severe toxicity. Here, the authors design a recombinant vaccinia virus expressing membrane-bound IL-2 that shows therapeutic efficacy alone or in combination with checkpoint inhibitors in colon cancer-bearing mice.
- Zuqiang Liu
- , Yan Ge
- & David L. Bartlett
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| Open AccessRe-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent
Interleukin-12 (IL-12) is a potent immunotherapeutic agent.
- Pengju Wang
- , Xiaozhu Li
- & Yaohe Wang
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| Open AccessResistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22
TGFβ secretion in the tumor microenvironment inhibits T cell-mediated anti-tumor immune responses. Here the authors show that a mutation predisposing to autoimmune diseases confers T cells resistance to TGFβ inhibitory action and could be exploited to engineer immunotherapies for TGFβ secreting tumors.
- Rebecca J. Brownlie
- , Celine Garcia
- & Rose Zamoyska
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| Open AccessEnhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells
Circulating memory cells include central memory T cells retaining the ability to enter the lymph nodes whereas tissue resident memory cells are confined to the parenchymal tissues. Here the authors explore the interplay between the two T-cell types and show that both cooperate in anti-tumour immunity.
- Michel Enamorado
- , Salvador Iborra
- & David Sancho
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| Open AccessNotch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy
Tumour-specific T cells can be expandedin vitroand adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.
- Taisuke Kondo
- , Rimpei Morita
- & Akihiko Yoshimura
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| Open AccessAdditives for vaccine storage to improve thermal stability of adenoviruses from hours to months
Keeping viral vaccines cold from the manufacturers to patients is problematic and costly. Here, Krol and others show additives that can significantly improve at very low concentrations the storage of adenovirus type 5 at ambient and elevated temperature.
- Maria Pelliccia
- , Patrizia Andreozzi
- & Silke Krol
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| Open AccessFollicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
T follicular regulatory cells control the magnitude of the germinal centre response. Here the authors show that these cells display specificity to self as well as foreign antigens, and can arise from Foxp3-negative precursors at early stages of immunization in a PD-L1 dependent manner.
- Meryem Aloulou
- , Edward J. Carr
- & Michelle A. Linterman
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| Open AccessProtective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Induction of protective immunity mediated by CD8+ T cells has been a long sought goal in vaccinology. Here, Ewer et al. report induction of protective efficacy against Plasmodium falciparummalaria in a phase IIa prime-boost vaccine trial where efficacy correlates strongly with induced CD8 T-cell responses.
- Katie J. Ewer
- , Geraldine A. O’Hara
- & Adrian V. S. Hill
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CD91-dependent programming of T-helper cell responses following heat shock protein immunization
Heat shock proteins bind to CD91 on antigen presenting cells, resulting in the presentation of chaperoned peptides to T cells. Here, heat shock protein binding is shown to induce phosphorylation of CD91 and stimulate the production of cytokines, thus priming various T-helper cell responses.
- Sudesh Pawaria
- & Robert J. Binder
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| Open AccessPandemic 2009 H1N1 vaccine protects against 1918 Spanish influenza virus
Vaccination against one viral strain can result in cross-reactive antibodies against another viral strain. In this study, the vaccination of mice against the 2009 H1N1 virus is shown to protect mice from the 1918 Spanish influenza virus, which resulted in millions of deaths worldwide.
- Rafael A. Medina
- , Balaji Manicassamy
- & Adolfo García-Sastre