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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 AccessGeneration of whole tumor cell vaccine for on-demand manipulation of immune responses against cancer under near-infrared laser irradiation
Whole autologous tumor cell vaccine (TCV) has been proposed as a tool for cancer immunotherapy. Here the authors describe the design of a TCV platform based on photothermal nanoparticle-loaded tumor cells, triggering NIR laser irradiation induced anti-tumor immune responses at the vaccination site.
- Jiaqi Meng
- , Yanlin Lv
- & Wei Wei
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| Open AccessA platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma
GM-CSF-secreting whole-cell cancer vaccine (GVAX) promotes T-cell response against a range of tumor associated antigens in patients with pancreatic adenocarcinoma (PDA). Here the authors report the results of the initial three treatment arms of a platform trial of neoadjuvant and adjuvant GVAX alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable PDA.
- Thatcher Heumann
- , Carol Judkins
- & Lei Zheng
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| Open AccessBacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity
Efferocytosis inhibition leads to the release of immunogenic contents into the tumor microenvironment. Here the authors developed a nanosystem that inhibits MerTK-mediated efferocytosis and captures tumor-associated agents to enhance antitumour immunity.
- Wan-Ru Zhuang
- , Yunfeng Wang
- & Hai-Yan Xie
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| Open AccessOncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity
Oncolytic viruses are able to target tumours and thought to induce apoptosis while remodelling the tumour immune microenvironment. Here authors show in an oncolytic parapoxvirus ovis model that pyroptosis, a highly immunogenic Gasdermin-E-dependent cell death mechanism, is the dominant cell death pathway during virotherapy.
- Jing Lin
- , Shihui Sun
- & Wenqi He
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| Open AccessEngineered Lactococcus lactis secreting Flt3L and OX40 ligand for in situ vaccination-based cancer immunotherapy
The probiotic Lactococcus lactis has been used for the delivery of therapeutic molecules. Here the authors engineer Lactococcus lactis to express a fusion protein of Flt3L and OX40 ligand, eliciting anti-tumor immune response in preclinical cancer models.
- Junmeng Zhu
- , Yaohua Ke
- & Baorui Liu
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| Open AccessExpanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity
Strategies to advance T cell based immune therapies are mostly focusing on the improvement of CD8 T cell effector functions, such as cytotoxicity or recruitment to the tumor. Here authors show that by combining in situ vaccination with oncolytic Newcastle Disease Virus and Flt3L-driven dendritic cell expansion, the anti-tumor T cell response is amplified via increased antigen cross-presentation.
- Judit Svensson-Arvelund
- , Sara Cuadrado-Castano
- & Joshua D. Brody
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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 AccessTumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape
The immunocytokine NHS-IL12 is targeted to necrotic tumour areas to prompt an immune response. Authors show here in mouse colon and breast models that the combination of histone deacetylase inhibitor, Entinostat, and NHS-IL12 generates a tumour microenvironment that favours tumour resolution.
- Kristin C. Hicks
- , Paul L. Chariou
- & Sofia R. Gameiro
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| Open AccessAdjuvant oncolytic virotherapy for personalized anti-cancer vaccination
Viruses expressing tumour antigens can prime and boost anti-tumour immunity but the efficiency of this approach depends on the capacity of the virus to infect the host. Here, the authors show that vaccination with oncolytic viruses co-administered with tumour antigenic peptides is as efficient as antigen-engineered oncolytic viruses.
- D. G. Roy
- , K. Geoffroy
- & M.-C. Bourgeois-Daigneault
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Article
| Open AccessPolycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window
Stimuli-responsive nanomaterials offer the opportunity to exploit nanoscale cooperativity to improve the precision of diagnostic or therapeutic outcomes. Here, the authors report the design, synthesis and characterization of a series of degradable ultra-pH sensitive polymers that amplify small acidic pH changes to efficacious therapeutic outputs.
- Xu Wang
- , Jonathan Wilhelm
- & Jinming Gao
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| Open AccessMelittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response
The bee venom melittin has anti-tumor properties but is unsuitable for therapeutic use on its own. Here, the authors generate melittin-nanoparticles and demonstrate that the nanoparticles reduce tumor growth and generate an anti-tumor immune response.
- Xiang Yu
- , Yanfeng Dai
- & Zhihong Zhang
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| Open AccessGenetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity
Experimental PVSRIPO oncolytic virus therapy of glioblastoma has shown long-term efficacy in a subset of patients. Here the authors engineer the virus to enable incorporation of tumor-specific antigens, and show proof-of-principle evidence that this modification increases anti-tumor immunity and extends survival in mice.
- Mubeen M. Mosaheb
- , Elena Y. Dobrikova
- & Matthias Gromeier
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| Open AccessA VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2
The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 patients, including in previously bevacizumab resistant tumors.
- Ryota Tamura
- , Masato Fujioka
- & Masahiro Toda
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| Open AccessAn inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases
Successful anticancer immunotherapy should induce robust systemic immunity against metastases. Here, the authors engineer an inhalable nano-STING agonist, which synergizes with fractionated radiation to control lung metastases and confers long-term systemic antitumor immunity in mice.
- Yang Liu
- , William N. Crowe
- & Dawen Zhao
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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 AccessAdenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade
Vaccination against neo-antigens has resulted in an effective antitumor response in several models. Here, the authors show that delivery of larger sets of neo-antigens using an adenovirus-based vaccination platform, results in much better tumor protection when combined with checkpoint blockade in a mouse model of advanced disease.
- Anna Morena D’Alise
- , Guido Leoni
- & Elisa Scarselli
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| Open AccessHuman preprocalcitonin self-antigen generates TAP-dependent and -independent epitopes triggering optimised T-cell responses toward immune-escaped tumours
Tumours can escape CD8 T-cell immunity by down-regulating antigen presentation machinery components, such as TAP. Here the authors describe tumour antigenic peptides processed by TAP-independent and -dependent pathways and show in mouse models that these peptides can be exploited to induce antitumor T-cell activity when TAP expression is downregulated.
- Aurélie Durgeau
- , Yasemin Virk
- & Fathia Mami-Chouaib
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| Open AccessAlbumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy
Albumin conjugates can enhance drug delivery. Here, the authors repurpose albumin-binding Evans blue to develop nanovaccines that co-deliver adjuvants and tumor neoantigens to antigen-presenting cells in lymph nodes, resulting in potent and durable antitumour immunity in combination immunotherapy.
- Guizhi Zhu
- , Geoffrey M. Lynn
- & Xiaoyuan Chen
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| Open AccessReplicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy
Viruses trigger potent cytotoxic T cell responses, whereas anti-tumour immunity has been difficult to establish. Here the authors engineer a replicating viral delivery system for tumour-associated antigens, which induces alarmin release, innate activation and protective anti-tumour immunity in mice.
- Sandra M. Kallert
- , Stephanie Darbre
- & Daniel D. Pinschewer
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| Open AccessPapilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice
Innate immunity sensors are expressed by both tumour cells and tumour-associated myeloid cells. Here, the authors show that stimulation of the innate immunity response with pseudoviruses in a genetic mouse model of intestinal cancer triggers tumour regression via Caspase-1 activation.
- Zhenyu Zhong
- , Yougang Zhai
- & Liang Qiao
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| Open AccessThe tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity
Dendritic cells are antigen-presenting cells consisting of distinct subsets originating from different lineages. Here, the authors identify the subsets of dendritic cells populating the tumour tissue in both mice and humans and find they have opposing functions in regulating the anti-tumour immune response.
- Damya Laoui
- , Jiri Keirsse
- & Jo A. Van Ginderachter