scholarly journals Future of cancer immunotherapy using plant virus-based nanoparticles

2019 ◽  
Vol 5 (7) ◽  
pp. FSO401 ◽  
Author(s):  
Erum Shoeb ◽  
Kathleen Hefferon

Immunotherapy potentiates a patient’s immune response against some forms of cancer, including malignant tumors. In this Special Report, we have summarized the use of nanoparticles that have been designed for use in cancer immunotherapy with particular emphasis on plant viruses. Plant virus-based nanoparticles are an ideal choice for therapeutic applications, as these nanoparticles are not only capable of targeting the desired cells but also of being safely delivered to the body without posing any threat of infection. Plant viruses can be taken up by tumor cells and can be functionalized as drug delivery vehicles. This Special Report describes how the future of cancer immunotherapy could be a success through the merger of computer-based technology using plant-virus nanoparticles.

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengguo Wu ◽  
Shang Li ◽  
Xiao Zhu

Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.


2004 ◽  
Vol 78 (10) ◽  
pp. 4976-4982 ◽  
Author(s):  
Ricardo B. Medeiros ◽  
Renato de O. Resende ◽  
Antonio Carlos de Ávila

ABSTRACT Tospoviruses have the ability to infect plants and their insect vectors. Tomato spotted wilt virus (TSWV), the type species in the Tospovirus genus, infects its most important insect vector, Frankliniella occidentalis, the western flower thrips (WFT). However, no detrimental effects on the life cycle or cytopathological changes have been reported in the WFT after TSWV infection, and relatively few viral particles can be observed even several days after infection. We hypothesized that TSWV infection triggers an immune response in the WFT. Using subtractive cDNA libraries to probe WFT DNA macroarrays, we found that the WFT's immune system is activated by TSWV infection. The activated genes included (i) those encoding antimicrobial peptides, such as defensin and cecropin; (ii) genes involved in pathogen recognition, such as those encoding lectins; (iii) those encoding receptors that activate the innate immune response, such as Toll-3; and (iv) those encoding members of signal transduction pathways activated by Toll-like receptors, such as JNK kinase. Transcriptional upregulation of these genes after TSWV infection was confirmed by Northern analysis, and the kinetics of the immune response was measured over time. Several of the detected genes were activated at the same time that viral replication was first detected by reverse transcription-PCR. To our knowledge, this is the first report of the activation of an insect vector immune response by a plant virus. The results may lead to a better understanding of insects' immune responses against viruses and may help in the future development of novel control strategies against plant viruses, as well as human and animal viruses transmitted by insect vectors.


2021 ◽  
Author(s):  
Haifang He ◽  
Jingjing Li ◽  
Zelong Zhang ◽  
Xuefei Tang ◽  
Danyang Song ◽  
...  

Abstract It is known that plant viruses, to facilitate their transmission, can change the phenotypes and defense pathways of the host plants and the performance of their vectors. Cucurbit chlorotic yellows virus (CCYV), a newly reported virus occurring on cucurbit plants and many other plant species, is transmitted specifically by Middle East-Minor Asia 1 (B biotype) and Mediterranean (Q biotype) cryptic species of whitefly, Bemisia tabaci (Gennadius), in a semipersistent manner. This study evaluated the direct and indirect effects of CCYV on B. tabaci biology to better understand the plant-virus-vector interaction. By using CCYV-B. tabaci-cucumber as the model, we investigated whether or how a semipersistent plant virus impacts the biology of its whitefly vectors. CCYV mRNA were detectable in nymphs from 1st to 4th instars and adults of B. tabaci with different titers. Female nymph duration and female adult longevity greatly extended on CCYV-infected plants, but male nymph duration and male adult longevity were not significantly influenced. In addition, on CCYV-infected plants, the body length and oviposition of adult B. tabaci increased, but the hatching rates of eggs and survival rates of different stages were not affected. Most interestingly, the sex ratio (male:female) significantly reduced to 0.506:1 in whitefly populations on CCYV-infected plants, while the ratio remained about 0.979:1 on healthy plants. These results indicated that CCYV can significantly impact the biological characteristics of its vector B. tabaci through the host plants. It is speculated that CCYV and B. tabaci have established a typical mutualist relationship mediated by host plants.


2019 ◽  
Vol 26 (33) ◽  
pp. 6132-6148 ◽  
Author(s):  
Noemi Arrighetti ◽  
Claudia Corbo ◽  
Michael Evangelopoulos ◽  
Anna Pastò ◽  
Valentina Zuco ◽  
...  

Cancer treatment still represents a formidable challenge, despite substantial advancements in available therapies being made over the past decade. One major issue is poor therapeutic efficacy due to lack of specificity and low bioavailability. The progress of nanotechnology and the development of a variety of nanoplatforms have had a significant impact in improving the therapeutic outcome of chemotherapeutics. Nanoparticles can overcome various biological barriers and localize at tumor site, while simultaneously protecting a therapeutic cargo and increasing its circulation time. Despite this, due to their synthetic origin, nanoparticles are often detected by the immune system and preferentially sequestered by filtering organs. Exosomes have recently been investigated as suitable substitutes for the shortcomings of nanoparticles due to their biological compatibility and particularly small size (i.e., 30-150 nm). In addition, exosomes have been found to play important roles in cell communication, acting as natural carriers of biological cargoes throughout the body. This review aims to highlight the use of exosomes as drug delivery vehicles for cancer and showcases the various attempts used to exploit exosomes with a focus on the delivery of chemotherapeutics and nucleic acids.


Author(s):  
Srividhya Venkataraman ◽  
Paul Apka ◽  
Erum Shoeb ◽  
Uzma Badar ◽  
Kathleen Hefferon

Plant virus nanoparticles (VNPs) are inexpensive to produce, safe, biodegradable and efficacious as treatments. The applications of r plant virus nanoparticles range from epitope carriers for vaccines to agents in cancer immunotherapy. Both VNPs and virus-like particles (VLPs) are highly immunogenic and are readily phagocytosed by antigen presenting cells (APCs), which in turn elicit antigen processing and display of pathogenic epitopes on their surfaces. Since the VLPs are composed of multiple copies of their respective capsid proteins, they present repetitive multivalent scaffolds which aid in antigen presentation. Therefore, the VLPs prove to be highly suitable platforms for delivery and presentation of antigenic epitopes, resulting in induction of more robust immune response compared to those of their soluble counterparts. Since the tumor microenvironment poses the challenge of self-antigen tolerance, VLPs are preferrable platforms for delivery and display of self-antigens as well as otherwise weakly immunogenic antigens. These properties, in addition to their diminutive size, enable the VLPs to deliver vaccines to the draining lymph nodes in addition to promoting APC interactions. Furthermore, many plant viral VLPs possess inherent adjuvant properties dispensing with the requirement of additional adjuvants to stimulate immune activity. Some of the highly immunogenic VLPs elicit innate immune activity, which in turn instigate adaptive immunity in tumor micro-environments. Plant viral VLPs are nontoxic, inherently stable, and capable of being mass-produced as well as being modified with antigens and drugs, therefore providing an attractive option for eliciting anti-tumor immunity. The following review explores the use of plant viruses as epitope carrying nanoparticles and as a novel tools in cancer immunotherapy.


2018 ◽  
Vol 99 (5) ◽  
pp. 792-801 ◽  
Author(s):  
E Yu Zlatnik ◽  
A O Sitkovskaya ◽  
E M Nepomnyashchaya ◽  
Ph R Dzhandigova ◽  
L N Vashchenko

This article reviews the immune system and its role in the relationship between the tumor and the body of a patient with tumor diseases. It is about controlling homeostasis by recognizing and eliminating genetically alien substances (antigens). Antitumor treatment is now not only considered as an “instrument” for eliminating and destroying tumor cells, but also its ability to change/restore impaired functions of the immune system attracts attention. The used antitumor treatment is widely known to be immunosuppressive, stress and radiation effects also cause and/or enhance immunosuppression. In this work, the authors provide literature data demonstrating current status and problems of cellular immunotherapy of malignant tumors with the use of activated lymphocytes, and the role of antigen-specific T-lymphocytes as one of its most important agents is reviewed. Currently, among the immunotherapeutic methods, a special place is occupied by approaches involving the use of autologous or allogenic ex vivo stimulated immunocompetent cells (adoptive immunotherapy). The importance of complex influence on various links (T-, B-, NK-cell) and stages (presentation, recognition, proliferation, differentiation, migration, activation, effector functions) of the immune response is considered. The emergence of targeted drugs based on antibodies, as well as vaccines, especially dendritic cells, has provoked the emergence of a new wave of interest in the formation of specific antitumoral immune response mediated by T lymphocytes, so the introduction of the latter can be classified as a kind of targeted therapy. The value of antigen-specific T-lymphocytes in the formation of antitumor immunity is shown, which emphasizes the importance not only of CD8+, but also of CD4+ T-lymphocytes. In addition, there are suggestions of the possible significance of both T- and B-cells for developing a strategy of cellular immunotherapy. The literature data suggest that not only cytotoxic lymphocytes, but also T-helpers and even B-lymphocytes can be effective as antigen-specific lymphocytes as a component of antitumor treatment. The authors consider the possibility of obtaining antigen-specific T cells, as well as their further storage. The possibility of elimination or selective inhibition of regulatory T-cells during adoptive immunotherapy aimed at removing the suppressor effect on cytotoxic lymphocytes is studied. Various strategies for the use of cell therapy are also discussed.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Linnan Yang ◽  
Feng Li ◽  
Yongsheng Cao ◽  
Qiang Liu ◽  
Guoxin Jing ◽  
...  

AbstractThe tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Austin B. Gardner ◽  
Simon K. C. Lee ◽  
Elliot C. Woods ◽  
Abhinav P. Acharya

The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, including macrophages, neutrophils, natural killer cells, T-cells, B-cells, and dendritic cells. Most often, these molecular signals lead to the generation of fibrous encapsulation of the biomaterials, thereby shielding the body from these biomaterials. In this review we will focus on two different types of biomaterials: those that actively modulate the immune response, as seen in antigen delivery vehicles for vaccines, and those that illicit relatively small immune response, which are important for implantable materials. The first serves to actively influence the immune response by co-opting certain immune pathways, while the second tries to mimic the properties of the host in an attempt to remain undetected by the immune system. As these are two very different end points, each type of biomaterial has been studied and developed separately and in recent years, many advances have been made in each respective area, which will be highlighted in this review.


2020 ◽  
Author(s):  
Haifang He ◽  
Jingjing Li ◽  
Zelong Zhang ◽  
Xuefei Tang ◽  
Danyang Song ◽  
...  

Abstract Background: It is known that plant viruses, to facilitate their transmission, can change the phenotypes and defense pathways of the host plants and thereby the performance of their vectors. Cucurbit chlorotic yellows virus (CCYV), a newly reported virus occurring on cucurbit plants and many other plant species, is transmitted specifically by B and Q biotypes of tobacco whitefly, Bemisia tabaci (Gennadius), in a semipersistent manner. This study evaluated the direct and indirect effects of CCYV on B. tabaci performance to better understand the plant-virus-vector interaction in terms of its impacts on the biological characteristics of its vector.Methods: In this study, by using CCYV-B. tabaci-cucumber as the model, we investigated whether or how a semipersistent plant virus impacts the biology of its whitefly vectors directly and/or indirectly. Virion titer, body size, life table parameters, survival rate of nymphs and adults, reproduction capacity of both adult sexes as well as sex ratio were compared between whiteflies on CCYV-infected plants and ones on healthy plants. Results: CCYV virions were detectable in nymphs from 1st to 4th instar and adults of B. tabaci with different titers. Female nymph duration and female adult longevity greatly extended on CCYV-infected plants, but male nymph duration and male adult longevity were not significantly influenced. In addition, on CCYV-infected plants, the body length and oviposition of adult B. tabaci increased, but the egg hatching rate and survival rate of different stages of the whiteflies were not affected. Most interestingly, the sex ratio (female:male) significantly increased up to 66.40% in whitefly populations on CCYV-infected plants, while the female ratio remained about 50.53% on healthy plants. Conclusions: These results indicated that CCYV can significantly impact the biological characteristics of its vector B. tabaci through the host plants. It is speculated that CCYV and B. tabaci have established a typical mutualist relationship mediated by host plants.


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