Biogenic particles can be multiantigenic, immunostimulative and activate innate immunity while suppressing tumor development

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Critical Role ◽  
Tumor Development ◽  
Host Cells ◽  
Delivery Technique ◽  
Biogenic Nanoparticles

Cancer immunotherapy, which attempts to activate or stimulate the immune system to treat cancer, has become the standard of treatment. Although some cancer vaccines are efficiently translated, they have not yet reached the same degree of success as infectious disease immunizations. A primary factor is the low immunogenicity of the tumor and related antigens. Unlike viruses, cancer cells emerge from somatic mutations in patients' healthy tissues, making it harder for the immune system to properly detect tumor cells. Biogenic nanoparticles have recently been highlighted as a solution to address some of the issues with creating anticancer vaccinations. Antigens, medication delivery, and others all benefit from biogenic nanoparticles. Biogenic nanoparticles have long been researched as a vaccine. Biogenic nanoparticles-based platforms, like particular VLPs, inherently activate inflammatory responses and may be increased with TAAs evaluated for antigen-specific antitumor responses to patient malignancies. OMVs and OMV-coated nanoparticles can be multiantigenic and immunostimulative in the box. PAMPs present in OMVs can activate innate immunity while suppressing tumor development. A range of cells, including immune and malignant cells, produce exosomes and play a critical role in cell-to-cell communication. Exosomes may contain interesting materials such as specific drugs, proteins, DNA, and RNA species, and their function depends on host cells. In cancer vaccines, however, these biogenic nanoparticles still have some limitations. Transferring tumor antigens and adjuvants to the secondary lymphoid system is a critical issue for biogenic nanoparticles. OMVs lack tumor antigens. Adjuvants are low in VLPs and exosomes. Furthermore, enhancing the protective response of biogenic nanoparticles, generating protective antigens in these nanoparticles and reducing the toxicity of nanoparticles are all challenges in cancer immunotherapy. There has been a lot of information regarding biogenic nanoparticles created by a variety of bacteria or cells in the area of bacterial vesicle research for a long time, but there has been a dearth of in-depth study focused on identifying molecules crucial to biogenesis or biogenic nanoparticles. Many basic questions remain unanswered here. Which envelope factors release biogenic nanoparticles? What signals and mechanisms regulate biogenic biogenic nanoparticles? Understanding these and other concepts as a cancer immunotherapy delivery technique is vital for the future development of biogenic nanoparticles. Future investigations are anticipated to begin to address these fundamental issues and increase our knowledge.

scholarly journals Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Wenjin Zheng ◽  
Qing Xu ◽  
Yiyuan Zhang ◽  
Xiaofei E ◽  
Wei Gao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Signaling Pathways ◽  
Critical Role ◽  
Innate Immune ◽  
Host Cells ◽  
Main Body ◽  
Current Perspective ◽  
Viral Components

Abstract Background In the past decades, researchers have demonstrated the critical role of Toll-like receptors (TLRs) in the innate immune system. They recognize viral components and trigger immune signal cascades to subsequently promote the activation of the immune system. Main body Herpesviridae family members trigger TLRs to elicit cytokines in the process of infection to activate antiviral innate immune responses in host cells. This review aims to clarify the role of TLRs in the innate immunity defense against herpesviridae, and systematically describes the processes of TLR actions and herpesviridae recognition as well as the signal transduction pathways involved. Conclusions Future studies of the interactions between TLRs and herpesviridae infections, especially the subsequent signaling pathways, will not only contribute to the planning of effective antiviral therapies but also provide new molecular targets for the development of antiviral drugs.

scholarly journals DC-Derived Exosomes for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3667
Author(s):  
Yi Yao ◽  
Chunmei Fu ◽  
Li Zhou ◽  
Qing-Sheng Mi ◽  
Aimin Jiang
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Clinical Efficacy ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Critical Role ◽  
Promising Alternative ◽  
Cell Immunity ◽  
Cancer Immunotherapies

As the initiators of adaptive immune responses, DCs play a central role in regulating the balance between CD8 T cell immunity versus tolerance to tumor antigens. Exploiting their function to potentiate host anti-tumor immunity, DC-based vaccines have been one of most promising and widely used cancer immunotherapies. However, DC-based cancer vaccines have not achieved the promised success in clinical trials, with one of the major obstacles being tumor-mediated immunosuppression. A recent discovery on the critical role of type 1 conventional DCs (cDC1s) play in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies, however, has highlighted the need to further develop and refine DC-based vaccines either as monotherapies or in combination with other therapies. DC-derived exosomes (DCexos) have been heralded as a promising alternative to DC-based vaccines, as DCexos are more resistance to tumor-mediated suppression and DCexo vaccines have exhibited better anti-tumor efficacy in pre-clinical animal models. However, DCexo vaccines have only achieved limited clinical efficacy and failed to induce tumor-specific T cell responses in clinical trials. The lack of clinical efficacy might be partly due to the fact that all current clinical trials used peptide-loaded DCexos from monocyte-derived DCs. In this review, we will focus on the perspective of expanding current DCexo research to move DCexo cancer vaccines forward clinically to realize their potential in cancer immunotherapy.

scholarly journals Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 668
Author(s):  
Howard Donninger ◽  
Chi Li ◽  
John W. Eaton ◽  
Kavitha Yaddanapudi
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Tumor Immunity ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Host Immune System ◽  
Tumor Type ◽  
Therapeutic Vaccines ◽  
Cancer Types ◽  
Prophylactic Vaccines

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.

scholarly journals The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3596
Author(s):  
Reza Bayat Mokhtari ◽  
Manpreet Sambi ◽  
Bessi Qorri ◽  
Narges Baluch ◽  
Neda Ashayeri ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Antigens ◽  
Response Rates ◽  
Viral Proteins ◽  
Tumor Rejection ◽  
Therapeutic Approaches ◽  
Patient Response ◽  
Specific Antigens

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.

scholarly journals Emerging nanomedicines for effective breast cancer immunotherapy

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Amirhossein Bahreyni ◽  
Yasir Mohamud ◽  
Honglin Luo
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Host Immune System ◽  
Primary Tumors ◽  
Novel Approach ◽  
Tumor Environment ◽  
Advanced Biomaterials

AbstractBreast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

A Critical Role for Innate Immunity In Allogeneic Hematopoietic Cell Rejection Via the TLR4/TRIF Pathway

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 77-77
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Ziqiang Zhu ◽  
Yiming Huang ◽  
Yujie Wen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Innate Immunity ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Innate Immune System ◽  
Critical Role ◽  
Innate Immune ◽  
Wild Type

Abstract Abstract 77 Adaptive immunity, especially T cells, has long been believed to be the dominant immune barrier in allogeneic transplantation. Targeting host T cells significantly reduces conditioning for bone marrow cell (BMC) engraftment. Innate immunity has been recently shown to pose a significant barrier in solid organ transplantation, but has not been addressed in bone marrow transplantation (BMT). Using T cell deficient (TCR-β/δ−/−) or T and B cell deficient (Rag−/−) mice, we found that allogeneic BMC rejection occurred early before the time required for T cell activation and was T- and B-cell independent, suggesting an effector role for innate immune cells in BMC rejection. Therefore, we hypothesized that by controlling both innate and adaptive immunity, the donor BMC would have a window of advantage to engraft. Survival of BMC in vivo was significantly improved by depleting recipient macrophages and/or NK cells, but not neutrophils. Moreover, depletion of macrophages and NK cells in combination with co-stimulatory blockade with anti-CD154 and rapamycin as a novel form of conditioning resulted in 100% allogeneic engraftment without any irradiation and T cell depletion. Donor chimerism remained stable and durable up to 6 months. Moreover, specific Vβ5½ and Vβ11 clonal deletion was detected in host CD4+ T cells in chimeras, indicating central tolerance to donor alloantigens. Whether and how the innate immune system recognizes or responds to allogeneic BMCs remains unknown. Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. The signaling function of TLR depends on intracellular adaptors. The adaptor MyD88 transmits signals emanating from all TLR, except TLR3 while TRIF specifically mediates TLR3 and TLR4 signaling via type 1 IFN. To further determine the innate signaling pathways in allogeneic BMC rejection, B6 background (H2b) MyD88−/− and TRIF−/− mice were conditioned with anti-CD154/rapamycin plus 100 cGy total body irradiation and transplanted with 15 × 106 BALB/c (H2d) BMC. Only 33.3% of MyD88−/− recipients engrafted at 1 month, resembling outcomes for wild-type B6 mice. In contrast, 100% of TRIF−/− mice engrafted. The level of donor chimerism in TRIF−/− mice was 5.1 ± 0.6% at one month, significantly higher than in MyD88−/− and wild-type B6 controls (P < 0.005). To determine the mechanism of innate signaling in BMC rejection, we examined whether TRIF linked TLR3 or TLR4 is the key pattern recognition receptor involved in BMC recognition. To this end, TLR3−/− and TLR4−/− mice were transplanted with BALB/c BMC with same conditioning. None of the TLR3−/− mice engrafted. In contrast, engraftment was achieved in 100% of TLR4−/− mice up to 6 months follow up. Taken together, these results suggest that rejection of allogeneic BMC is uniquely dependent on the TLR4/TRIF signaling pathway. Thus, our results clearly demonstrate a previously unappreciated role for innate immunity in allogeneic BMC rejection. Our current findings are distinct from prior reports demonstrating a critical role of MyD88 in rejection of allogeneic skin grafts and lung, and may reflect unique features related to BMC. The findings of the role of innate immunity in BMC rejection would lead to revolutionary changes in our understanding and management of BMT. This would be informative in design of more specific innate immune targeted conditioning proposals in BMT to avoid the toxicity. Disclosures: Bozulic: Regenerex LLC: Employment. Ildstad:Regenerex LLC: Equity Ownership.

Application of Nanocomposites in Cancer Immunotherapy

Nano LIFE ◽  
2017 ◽  
Vol 07 (03n04) ◽  
pp. 1750008
Author(s):  
Wenhan Liu ◽  
Zejun Wang ◽  
Yao Luo ◽  
Nan Chen
Keyword(s):  
Immune System ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Critical Role ◽  
Clinical Advances ◽  
Review Current

Despite the clinical advances in oncology, cancer is still the major cause of death worldwide. Recent research demonstrates that the immune system plays a critical role in preventing tumor occurrence and development. The focus on cancer treatment has been shifted from directly targeting the tumor cells to motivating the immune system to achieve this goal. However, the activity of immune system is often suppressed in cancer patients. To boost the anti-tumor immunity against cancers, various nanocomposites have been developed to enhance the efficacy of immunostimulatory agents. Here, we review current advances in nanomaterial-mediated immunotherapy for the treatment of cancer, with an emphasis on applications of nanocomposites as immunoadjuvants in cancer therapy.

Cancer Immunotherapy: An Effective Tool in Cancer Control and Treatment

2020 ◽  
Vol 16 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Kawalpreet Kaur ◽  
Gopal L. Khatik
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
Cancer Control ◽  
The Body ◽  
Active Immunotherapy ◽  
Natural Immunity ◽  
Passive Immunotherapy ◽  
Scientific Database

Background:: Cancer immunotherapy is a type of cancer treatment which effectively harnesses the natural ability of the immune system to fight against cancer cells. This approach takes into consideration the fact that cancer cells express various types of antigens on their surface. Such tumor antigens can be detected by the immune system. However, cancer cells normally develop resistance to the defensive mechanisms presented by the immune system. Thus, cancer immunotherapy has some challenges in its path but due to its impressive clinical effectiveness, it is considered as the potential and effective mode of treatment for cancer. Methods:: We searched the scientific database using cancer, immunotherapy, and tumor antigens as the keywords. Herein, only peer-reviewed research articles were collected which were useful to our current work. Results:: Cells responsible for incurring natural immunity to the body are engineered in such a way that they become able to efficiently recognize and bind to tumor antigens. Such type of immunotherapy is referred to as active immunotherapy. Another type is passive immunotherapy, which involves the process of modifying the existing natural immune responses against cancer cells. A hybrid type of immunotherapy has also been developed which involves the combinative use of both active and passive immunotherapy. Cancer immunotherapy has so far proven to be an effective treatment for cancer as this therapy primarily aims at attacking cancer cells and not the healthy body cells lying in close vicinity to them. Conclusion:: In the review, we described the significance of immunotherapy in the management of various types of cancer.

scholarly journals Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Zhe Zou ◽  
Zhihua Meng ◽  
Chao Ma ◽  
Deguang Liang ◽  
Rui Sun ◽  
...  
Keyword(s):  
Immune System ◽  
Actin Filaments ◽  
Primary Infection ◽  
Rna Viruses ◽  
Critical Role ◽  
Host Cells ◽  
Host Immune System ◽  
Kshv Infection ◽  
Guanylate Binding Protein

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. In order to establish successful infection, KSHV has evolved numerous immune evasion strategies to bypass or hijack the host immune system. However, host cells still produce immune cytokines abundantly during primary KSHV infection. Whether the immune effectors produced are able to inhibit viral infection and how KSHV successfully conquers these immune effectors remain largely unknown. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on several RNA viruses; however, its function in DNA virus infection is less well understood. In this study, we found that KSHV infection increases both the transcriptional and protein levels of GBP1 at the early stage of primary infection by activating the NF-κB pathway. The overexpression of GBP1 significantly inhibited KSHV infection, while the knockdown of GBP1 promoted KSHV infection. The GTPase activity and dimerization of GBP1 were demonstrated to be responsible for its anti-KSHV activity. Furthermore, we found that GBP1 inhibited the nuclear delivery of KSHV virions by disrupting the formation of actin filaments. Finally, we demonstrated that replication and transcription activator (RTA) promotes the degradation of GBP1 through a proteasome pathway. Taken together, these results provide a new understanding of the antiviral mechanism of GBP1, which possesses potent anti-KSHV activity, and suggest the critical role of RTA in the evasion of the innate immune response during primary infection by KSHV. IMPORTANCE GBP1 can be induced by various cytokines and exerts antiviral activities against several RNA viruses. Our study demonstrated that GBP1 can exert anti-KSHV function by inhibiting the nuclear delivery of KSHV virions via the disruption of actin filaments. Moreover, we found that KSHV RTA can promote the degradation of GBP1 through a proteasome-mediated pathway. Taken together, our results elucidate a novel mechanism of GBP1 anti-KSHV activity and emphasize the critical role of RTA in KSHV evasion of the host immune system during primary infection.

scholarly journals Role of Intestinal Alkaline Phosphatase in Innate Immunity

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1784
Author(s):  
Sudha B. Singh ◽  
Henry C. Lin
Keyword(s):  
Innate Immunity ◽  
Alkaline Phosphatase ◽  
Critical Role ◽  
Host Cells ◽  
Immune Functions ◽  
Intestinal Alkaline Phosphatase ◽  
Functional Protein ◽  
Mammalian Cell Lines ◽  
Defensive Role

Intestinal alkaline phosphatase (IAP) is a multi-functional protein that has been demonstrated to primarily protect the gut. The role of IAP in maintaining intestinal homeostasis is underscored by the observation that IAP expression is defective in many gastrointestinal-related disorders such as inflammatory bowel disease IBD, necrotizing enterocolitis, and metabolic syndrome and that exogenous IAP supplementation improves the outcomes associated with these disorders. Additionally, studies using transgenic IAP-knock out (IAP-KO) mouse models further support the importance of the defensive role of IAP in the intestine. Supplementation of exogenous IAP and cellular overexpression of IAP have also been used in vitro to dissect out the downstream mechanisms of this protein in mammalian cell lines. Some of the innate immune functions of IAP include lipopolysaccharide (LPS) detoxification, protection of gut barrier integrity, regulation of gut microbial communities and its anti-inflammatory roles. A novel function of IAP recently identified is the induction of autophagy. Due to its critical role in the gut physiology and its excellent safety profile, IAP has been used in phase 2a clinical trials for treating conditions such as sepsis-associated acute kidney injury. Many excellent reviews discuss the role of IAP in physiology and pathophysiology and here we extend these to include recent updates on this important host defense protein and discuss its role in innate immunity via its effects on bacteria as well as on host cells. We will also discuss the relationship between IAP and autophagy and how these two pathways may act in concert to protect the gut.

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