STING activation in cancer immunotherapy DOI Creative Commons
Ting Su, Yu Zhang, Kristoffer Valerie

et al.

Theranostics, Journal Year: 2019, Volume and Issue: 9(25), P. 7759 - 7771

Published: Jan. 1, 2019

Cancer immunotherapy modulates and leverages the host immune system to treat cancer. The past decade has witnessed historical advancement of cancer immunotherapy. A myriad approaches have been explored elicit or augment anticancer innate immunity and/or adaptive immunity. Recently, activation stimulator interferon (IFN) genes (STING), an intracellular receptor residing in endoplasmic reticulum, shown great potential enhance antitumor through induction a variety pro-inflammatory cytokines chemokines, including type I IFNs. number natural synthetic STING agonists discovered developed, tested preclinical models clinic for diseases such as infectious diseases. Cyclic dinucleotides (CDNs), cyclic dimeric guanosine monophosphate (c-di-GMP), adenosine (c-di-AMP), GMP-AMP (cGAMP), are class that can responses. However, CDNs hydrophilic small molecules with negative charges susceptible enzymatic degradation, leading low bioavailability target tissues yet unwanted toxicities narrow therapeutic windows. Drug delivery systems, coupled nucleic acid chemistry, exploited address these challenges. Here, we will discuss underlying immunological mechanisms activation, focus on agonists,

Language: Английский

Delivery technologies for cancer immunotherapy DOI
Rachel Riley, Carl H. June, Róbert Langer

et al.

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(3), P. 175 - 196

Published: Jan. 8, 2019

Language: Английский

Citations

2129

In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment DOI
Qian Chen, Chao Wang, Xudong Zhang

et al.

Nature Nanotechnology, Journal Year: 2018, Volume and Issue: 14(1), P. 89 - 97

Published: Dec. 4, 2018

Language: Английский

Citations

853

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment DOI
Guoyou Huang, Fei Li, Xin Zhao

et al.

Chemical Reviews, Journal Year: 2017, Volume and Issue: 117(20), P. 12764 - 12850

Published: Oct. 9, 2017

The cell microenvironment has emerged as a key determinant of behavior and function in development, physiology, pathophysiology. extracellular matrix (ECM) within the serves not only structural foundation for cells but also source three-dimensional (3D) biochemical biophysical cues that trigger regulate behaviors. Increasing evidence suggests 3D character is required development many critical responses observed vivo, fueling surge functional biomimetic materials engineering microenvironment. Progress design such improved control behaviors advanced fields tissue regeneration, vitro models, large-scale differentiation, immunotherapy, gene therapy. However, field still its infancy, discoveries about nature cell–microenvironment interactions continue to overturn much early progress field. Key challenges be dissecting roles chemistry, structure, mechanics, electrophysiology microenvironment, understanding harnessing periodicity drift these factors. This review encapsulates where recent advances appear leave ever-shifting state art, it highlights areas which substantial potential uncertainty remain.

Language: Английский

Citations

676

Cancer Cell Membrane-Coated Adjuvant Nanoparticles with Mannose Modification for Effective Anticancer Vaccination DOI
Rong Yang, Jun Xu, Ligeng Xu

et al.

ACS Nano, Journal Year: 2018, Volume and Issue: 12(6), P. 5121 - 5129

Published: May 17, 2018

Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of immunotherapy recent years. In this work, we present a strategy to construct by encapsulating immune-adjuvant nanoparticles with cell membranes modified mannose. Poly(d,l-lactide-co-glycolide) are first loaded toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant (NP-R) then coated (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification mannose moiety (NP-R@M-M), obtained nanovaccine shows enhanced uptake antigen presenting cells such dendritic cells, which would be stimulated maturation status trigger antitumor immune responses. great efficacy delay tumor development vaccine, vaccination NP-R@M-M combination checkpoint-blockade therapy demonstrates outstanding therapeutic treat established tumors. Therefore, our work presents an innovative way fabricate nanovaccines, principle may applied wide range types.

Language: Английский

Citations

631

In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy DOI Open Access
Chao Wang, Jinqiang Wang, Xudong Zhang

et al.

Science Translational Medicine, Journal Year: 2018, Volume and Issue: 10(429)

Published: Feb. 21, 2018

Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) distinct kinetics. The consists reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics manner within tumor microenvironment (TME), which contains abundant ROS. found aPDL1-GEM elicits immunogenic phenotype promotes immune-mediated regression tumor-bearing mice, prevention recurrence after primary resection.

Language: Английский

Citations

514

Massively Evoking Immunogenic Cell Death by Focused Mitochondrial Oxidative Stress using an AIE Luminogen with a Twisted Molecular Structure DOI
Chao Chen, Xiang Ni,

Shaorui Jia

et al.

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(52)

Published: Nov. 7, 2019

Immunogenic cell death (ICD) provides momentous theoretical principle for modern cancer immunotherapy. However, the currently available ICD inducers are still very limited and photosensitizer-based ones can hardly induce sufficient to achieve satisfactory immunotherapy by themselves. Herein, an organic photosensitizer (named TPE-DPA-TCyP) with a twisted molecular structure, strong aggregation-induced emission activity, specific ability is reported effectively inducing focused mitochondrial oxidative stress of cells, which serve as much superior inducer popularly used ones, including chlorin e6 (Ce6), pheophorbide A, oxaliplatin. Furthermore, more effective in vivo immunogenicity TPE-DPA-TCyP than Ce6 also demonstrated using prophylactic tumor vaccination model. The underlying mechanism effectiveness robustness antitumor immunity immune-memory effect verified immune analyses. This study thus reveals that highly strategy evoke abundant large-scale ICD.

Language: Английский

Citations

462

A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy DOI Open Access
Jun Xu, Jia Lv,

Qi Zhuang

et al.

Nature Nanotechnology, Journal Year: 2020, Volume and Issue: 15(12), P. 1043 - 1052

Published: Nov. 2, 2020

Language: Английский

Citations

448

Precise nanomedicine for intelligent therapy of cancer DOI
Huabing Chen, Zhanjun Gu, Hong‐Wei An

et al.

Science China Chemistry, Journal Year: 2018, Volume and Issue: 61(12), P. 1503 - 1552

Published: Dec. 1, 2018

Language: Английский

Citations

390

Combining Nanomedicine and Immunotherapy DOI
Yang Shi, Twan Lammers

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(6), P. 1543 - 1554

Published: May 23, 2019

ConspectusNanomedicine holds significant potential to improve the efficacy of cancer immunotherapy. Thus far, nanomedicines, i.e., 1–100(0) nm sized drug delivery systems, have been primarily used balance between and toxicity conjugated or entrapped chemotherapeutic drugs. The clinical performance nanomedicines has somewhat disappointing, which is arguably mostly due lack tools technologies for patient stratification. Conversely, progress made with immunotherapy spectacular, achieving complete cures inducing long-term survival in advanced-stage patients. Unfortunately, however, only works well relatively small subsets Increasing amounts preclinical data demonstrate that combining nanomedicine can boost therapeutic outcomes, by turning "cold" nonimmunoresponsive tumors metastases into "hot" immunoresponsive lesions.Nano-immunotherapy be realized via three different approaches, are (1) target cells, (2) tumor immune microenvironment, (3) peripheral system. When targeting typically aim induce immunogenic cell death, thereby triggering release antigens danger-associated molecular patterns, such as calreticulin translocation, high mobility group box 1 protein adenosine triphosphate. latter serve adjuvants alert antigen-presenting cells take up, process present former, promoting generation CD8+ cytotoxic T cells. Nanomedicines microenvironment potentiate inhibiting immunosuppressive M2-like tumor-associated macrophages, reducing expression molecules, transforming growth factor beta. In addition, employed promote activity microenvironment. system enhance antigen presentation production secondary lymphoid organs, lymph nodes spleen, engineer strengthen effector populations, anticancer immunity.While majority immunomodulatory development, exciting results already reported initial trials. To ensure efficient translation nano-immunotherapy constructs concepts, we consider biomarkers their make sure right formulation combined patient. this context, learn from currently ongoing efforts nano-biomarker identification partially established immuno-biomarker initiatives, Immunoscore immunogram. Together, these protocols will help capture nano-immuno status individual patients, enabling use individualized improved nanomedicine-based treatments

Language: Английский

Citations

390

Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells DOI
Qian Chen, Quanyin Hu, Elena Dukhovlinova

et al.

Advanced Materials, Journal Year: 2019, Volume and Issue: 31(23)

Published: March 27, 2019

Chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and immunosuppressive microenvironment usually account for reduced CAR cells Mild hyperthermia reduces its compact interstitial fluid pressure, increases blood perfusion, releases antigens, promotes recruitment endogenous immune cells. Therefore, combination mild with adoptive transfer can potentially increase index these It is found that chondroitin sulfate proteoglycan-4 (CSPG4)-specific infused Nod scid gamma mice engrafted human melanoma WM115 cell line have superior antitumor activity after photothermal ablation tumor. findings suggest therapy facilitates accumulation effector function within

Language: Английский

Citations

389