scholarly journals Self-healing microcapsules synergetically modulate immunization microenvironments for potent cancer vaccination

2020 ◽  
Vol 6 (21) ◽  
pp. eaay7735 ◽  
Author(s):  
Xiaobo Xi ◽  
Tong Ye ◽  
Shuang Wang ◽  
Xiangming Na ◽  
Jianghua Wang ◽  
...  

Therapeutic cancer vaccines that harness the immune system to reject cancer cells have shown great promise for cancer treatment. Although a wave of efforts have spurred to improve the therapeutic effect, unfavorable immunization microenvironment along with a complicated preparation process and frequent vaccinations substantially compromise the performance. Here, we report a novel microcapsule-based formulation for high-performance cancer vaccinations. The special self-healing feature provides a mild and efficient paradigm for antigen microencapsulation. After vaccination, these microcapsules create a favorable immunization microenvironment in situ, wherein antigen release kinetics, recruited cell behavior, and acid surrounding work in a synergetic manner. In this case, we can effectively increase the antigen utilization, improve the antigen presentation, and activate antigen presenting cells. As a result, effective T cell response, potent tumor inhibition, antimetastatic effects, and prevention of postsurgical recurrence are achieved with various types of antigens, while neoantigen was encapsuled and evaluated in different tumor models.

2019 ◽  
Vol 7 (47) ◽  
pp. 27048-27056 ◽  
Author(s):  
Weiqiang Kong ◽  
Zhongsheng Wen ◽  
Zhaoyang Zhou ◽  
Guanqin Wang ◽  
Jinpeng Yin ◽  
...  

Phosphorous–sulfur/carbon composite sulfur is strategically incorporated with phosphorous by P–S bonding. The formed solvable Li–S intermediates could be anchored on the surface of phosphorous by capillary and thus heal the cracks/defects.


1990 ◽  
Vol 172 (2) ◽  
pp. 631-640 ◽  
Author(s):  
K Inaba ◽  
J P Metlay ◽  
M T Crowley ◽  
R M Steinman

T cells recognize peptides that are bound to MHC molecules on the surface of different types of antigen-presenting cells (APC). Antigen presentation most often is studied using T cells that have undergone priming in situ, or cell lines that have been chronically stimulated in vitro. The use of primed cells provides sufficient numbers of antigen-reactive lymphocytes for experimental study. A more complete understanding of immunogenicity, however, requires that one develop systems for studying the onset of a T cell response from unprimed lymphocytes, especially in situ. Here it is shown that mouse T cells can be reliably primed in situ using dendritic cells as APC. The dendritic cells were isolated from spleen, pulsed with protein antigens, and then administered to naive mice. Antigen-responsive T cells developed in the draining lymphoid tissue, and these T cells only recognized protein when presented on cells bearing the same MHC products as the original priming dendritic cells. In contrast, little or no priming was seen if antigen-pulsed spleen cells or peritoneal cells were injected. Since very small amounts of the foreign protein were visualized within endocytic vacuoles of antigen-pulsed dendritic cells, it is suggested that dendritic cells have a small but relevant vacuolar system for presenting antigens over a several day period in situ.


2018 ◽  
Vol 47 (37) ◽  
pp. 13126-13134 ◽  
Author(s):  
Shi-Cheng Wang ◽  
Minli Gu ◽  
Luqing Pan ◽  
Junfeng Xu ◽  
Lei Han ◽  
...  

High-quality graphene@prussian blue (G@PB) nanocomposite sheets fabricated via the one-step in situ hydrothermal method show great promise for energy-storage hybrid electrodes with excellent electrochemical performance.


2021 ◽  
Author(s):  
Cécile Chazot ◽  
Behzad Damirchi ◽  
Adri van Duin ◽  
John Hart

Molecularly organized nanocomposites of polymers and carbon nanotubes (CNTs) have great promise as high-performance materials; in particular, conformal deposition of polymers can control interfacial properties for mechanical load transfer, electrical or thermal transport, or electro/chemical transduction. However, controllability of polymer-CNT interaction remains a challenge with common processing methods that combine CNTs and polymers in melt or in solution, often leading to non-uniform polymer distribution and/or aggregation of CNTs. Here, we demonstrate CNTs within net-shape sheets can be controllably coated with a thin, conformal coating of meta-aramid by simultaneous capillary infiltration and interfacial polymerization. We determine that π interaction between the polymer and CNTs results in chain alignment parallel to the CNT outer wall. Subsequent nucleation and growth of the precipitated aramid forms a smooth continuous layered sheath around the CNTs. These findings motivate future investigation of mechanical and interfacial properties of the resulting CNT composites, and adaptation of the in-situ polymerization method to other substrates.


Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 615 ◽  
Author(s):  
Luigi Buonaguro ◽  
Maria Tagliamonte

One of the principal goals of cancer immunotherapy is the development of efficient therapeutic cancer vaccines that are able to elicit an effector as well as memory T cell response specific to tumor antigens. In recent years, the attention has been focused on the personalization of cancer vaccines. However, the efficacy of therapeutic cancer vaccines is still disappointing despite the large number of vaccine strategies targeting different tumors that have been evaluated in recent years. While the preclinical data have frequently shown encouraging results, clinical trials have not provided satisfactory data to date. The main reason for such failures is the complexity of identifying specific target tumor antigens that should be unique or overexpressed only by the tumor cells compared to normal cells. Most of the tumor antigens included in cancer vaccines are non-mutated overexpressed self-antigens, eliciting mainly T cells with low-affinity T cell receptors (TCR) unable to mediate an effective anti-tumor response. In this review, the target tumor antigens employed in recent years in the development of therapeutic cancer vaccine strategies are described, along with potential new classes of tumor antigens such as the human endogenous retroviral elements (HERVs), unconventional antigens, and/or heteroclitic peptides.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1049 ◽  
Author(s):  
Anna Lucia Tornesello ◽  
Maria Tagliamonte ◽  
Maria Lina Tornesello ◽  
Franco M. Buonaguro ◽  
Luigi Buonaguro

Nanoparticles represent a potent antigen presentation and delivery system to elicit an optimal immune response by effector cells targeting tumor-associated antigens expressed by cancer cells. Many types of nanoparticles have been developed, such as polymeric complexes, liposomes, micelles and protein-based structures such as virus like particles. All of them show promising results for immunotherapy approaches. In particular, the immunogenicity of peptide-based cancer vaccines can be significantly potentiated by nanoparticles. Indeed, nanoparticles are able to enhance the targeting of antigen-presenting cells (APCs) and trigger cytokine production for optimal T cell response. The present review summarizes the categories of nanoparticles and peptide cancer vaccines which are currently under pre-clinical evaluation.


2021 ◽  
Author(s):  
Cécile Chazot ◽  
Behzad Damirchi ◽  
Adri van Duin ◽  
John Hart

Molecularly organized nanocomposites of polymers and carbon nanotubes (CNTs) have great promise as high-performance materials; in particular, conformal deposition of polymers can control interfacial properties for mechanical load transfer, electrical or thermal transport, or electro/chemical transduction. However, controllability of polymer-CNT interaction remains a challenge with common processing methods that combine CNTs and polymers in melt or in solution, often leading to non-uniform polymer distribution and/or aggregation of CNTs. Here, we demonstrate CNTs within net-shape sheets can be controllably coated with a thin, conformal coating of meta-aramid by simultaneous capillary infiltration and interfacial polymerization. We determine that π interaction between the polymer and CNTs results in chain alignment parallel to the CNT outer wall. Subsequent nucleation and growth of the precipitated aramid forms a smooth continuous layered sheath around the CNTs. These findings motivate future investigation of mechanical and interfacial properties of the resulting CNT composites, and adaptation of the in-situ polymerization method to other substrates.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4053 ◽  
Author(s):  
Hui Kian Ong ◽  
Wen Siang Tan ◽  
Kok Lian Ho

Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative. In addition, they can be engineered to display multiple, highly ordered heterologous epitopes or peptides in order to optimize the antigenicity and immunogenicity of the displayed entities. Like native viruses, specific epitopes displayed on VLPs can be taken up, processed, and presented by antigen-presenting cells to elicit potent specific humoral and cell-mediated immune responses. Several studies also indicated that VLPs could overcome the immunosuppressive state of the tumor microenvironment and break self-tolerance to elicit strong cytotoxic lymphocyte activity, which is crucial for both virus clearance and destruction of cancerous cells. Collectively, these unique characteristics of VLPs make them optimal cancer vaccine candidates. This review discusses current progress in the development of VLP-based cancer vaccines and some potential drawbacks of VLPs in cancer vaccine development. Extracellular vesicles with close resembling to viral particles are also discussed and compared with VLPs as a platform in cancer vaccine developments.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1463
Author(s):  
Stefania Cuzzubbo ◽  
Antoine F. Carpentier

Thanks to the growing knowledge about cancers and their interactions with the immune system, a huge number of therapeutic cancer vaccines have been developed in the past two decades. Despite encouraging results in pre-clinical models, cancer vaccines have not yet achieved significant clinical efficacy. Several factors may contribute to such poor results, including the difficulty of triggering a strong immune response and the immunosuppressive tumor microenvironment. Many strategies are currently being explored. Different types of adjuvants have been incorporated into vaccine formulations to improve their efficacy, as cancer antigens are usually poorly immunogenic. Nanoparticle systems are promising tools as they act as carriers for antigens and can be surface-modified so that they specifically target antigen-presenting cells in lymph nodes. Bioinspired nanomaterials are ideal candidates thanks to their biocompatibility. Recently, melanin-based nanoparticles were reported to efficiently localize into draining lymphoid tissues and trigger immune responses against loaded antigens. In addition, by virtue of their photochemical properties, melanin-based nanoparticles can also play an immunomodulatory role to promote anti-cancer responses in the context of photothermal therapy. In this review, we discuss the above-mentioned properties of melanin, and summarize the promising results of the melanin-based cancer vaccines recently reported in preclinical models.


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