Exosome-based immunotherapy: a promising approach for cancer treatment

Abstract In the era of the rapid development of cancer immunotherapy, there is a high level of interest in the application of cell-released small vesicles that stimulate the immune system. As cell-derived nanovesicles, exosomes show great promise in cancer immunotherapy because of their immunogenicity and molecular transfer function. The cargoes carried on exosomes have been recently identified with improved technological advances and play functional roles in the regulation of immune responses. In particular, exosomes derived from tumor cells and immune cells exhibit unique composition profiles that are directly involved in anticancer immunotherapy. More importantly, exosomes can deliver their cargoes to targeted cells and thus influence the phenotype and immune-regulation functions of targeted cells. Accumulating evidence over the last decade has further revealed that exosomes can participate in multiple cellular processes contributing to cancer development and therapeutic effects, showing the dual characteristics of promoting and suppressing cancer. The potential of exosomes in the field of cancer immunotherapy is huge, and exosomes may become the most effective cancer vaccines, as well as targeted antigen/drug carriers. Understanding how exosomes can be utilized in immune therapy is important for controlling cancer progression; additionally, exosomes have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer.

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Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms221910219 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10219

Author(s):

Shirin Hafezi ◽

Maha Saber-Ayad ◽

Wael M. Abdel-Rahman

Keyword(s):

Pancreatic Cancer ◽

Cancer Progression ◽

Human Cancer ◽

Ductal Adenocarcinoma ◽

Ras Gene ◽

Kras Mutations ◽

Oncogenic Mutations ◽

History Of ◽

Novel Therapeutic Strategies ◽

The Impact

The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets.

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Analisis Forensik Smartphone Android Menggunakan Metode NIST dan Tool MOBILedit Forensic Express

Jurnal Informatika Universitas Pamulang ◽

10.32493/informatika.v5i1.4578 ◽

2020 ◽

Vol 5 (1) ◽

pp. 89

Author(s):

Nasirudin Nasirudin ◽

Sunardi Sunardi ◽

Imam Riadi

Keyword(s):

Mobile Device ◽

Rapid Development ◽

Rapid Progress ◽

Data Backup ◽

Technological Advances ◽

Smartphone Technology ◽

Case Simulation ◽

Device Technology

Technological advances are growing rapidly, including mobile device technology, one of which is an Android smartphone that is experiencing rapid progress with a variety of features so that it can spoil its users, with the rapid development of smartphone technology, many users benefit, but many are disadvantaged by the growing smartphone. technology, so that many perpetrators or persons who commit crimes and seek profits with smartphone facilities. Case simulation by securing Samsung Galaxy A8 brand android smartphone evidence using the MOBILedit forensic express forensic tool with the National Institute of Standards and Technology (NIST) method which consists of four stages of collection, examination, analysis and reporting. The results of testing the Samsung Galaxy A8 android smartphone are carried out with the NIST method and the MOBILedit Forensic Express tool obtained by data backup, extraction and analysis so that there are findings sought for investigation and evidence of crimes committed by persons using android smartphone facilities.

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Role of MicroRNAs in Colon Cancer Progression and Metastasis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200825184924 ◽

2020 ◽

Vol 20 ◽

Author(s):

Shruthi Sanjitha Sampath ◽

Sivaramakrishnan Venkatabalsubramanian ◽

Satish Ramalingam

Keyword(s):

Colon Cancer ◽

Cancer Progression ◽

Target Genes ◽

Tumour Progression ◽

Intestinal Barrier ◽

Colon Cancer Progression ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

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Current RNA-based Therapeutics in Clinical Trials

Current Gene Therapy ◽

10.2174/1566523219666190719100526 ◽

2019 ◽

Vol 19 (3) ◽

pp. 172-196 ◽

Cited By ~ 15

Author(s):

Ling-Yan Zhou ◽

Zhou Qin ◽

Yang-Hui Zhu ◽

Zhi-Yao He ◽

Ting Xu

Keyword(s):

Clinical Trials ◽

Rapid Development ◽

Genetic Diseases ◽

Three Dimensional ◽

Therapeutic Effects ◽

Messenger Rnas ◽

Small Interfering Rnas ◽

Rna Modifications ◽

Guide Rna ◽

Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

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Transporter associated with antigen processing 1 (TAP1) expression and prognostic analysis in breast, lung, liver, and ovarian cancer

Journal of Molecular Medicine ◽

10.1007/s00109-021-02088-w ◽

2021 ◽

Author(s):

Anika Tabassum ◽

Md. Nazmus Samdani ◽

Tarak Chandra Dhali ◽

Rahat Alam ◽

Foysal Ahammad ◽

...

Keyword(s):

Expression Pattern ◽

Cancer Progression ◽

Antigen Processing ◽

Human Cancer ◽

Analytical Data ◽

Significant Negative Correlation ◽

Cancer Tissue ◽

Human Cancer Cell Lines ◽

Prognostic Analysis ◽

Cancer Types

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

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SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5088 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 934.3-934

Author(s):

M. Kim ◽

Y. Choe ◽

H. Lee ◽

Y. H. Cheon ◽

S. I. Lee

Keyword(s):

Rheumatoid Arthritis ◽

Cancer Progression ◽

Inflammatory Responses ◽

Joint Destruction ◽

Serum Levels ◽

Therapeutic Effects ◽

Collagen Induced Arthritis ◽

Translationally Controlled Tumor Protein ◽

Biochemical Analyses ◽

Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

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Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02389-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ruijie Zeng ◽

Jinghua Wang ◽

Zewei Zhuo ◽

Yujun Luo ◽

Weihong Sha ◽

...

Keyword(s):

Stem Cells ◽

Necrotizing Enterocolitis ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Pediatric Diseases ◽

Gastrointestinal Conditions ◽

Different Types ◽

Novel Therapeutic Strategies

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.

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Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Cancers ◽

10.3390/cancers13020326 ◽

2021 ◽

Vol 13 (2) ◽

pp. 326

Author(s):

Dona Sinha ◽

Sraddhya Roy ◽

Priyanka Saha ◽

Nabanita Chatterjee ◽

Anupam Bishayee

Keyword(s):

Cancer Progression ◽

Targeted Delivery ◽

Cancer Biology ◽

Vaccine Development ◽

Immune Escape ◽

Immune Therapy ◽

Bioactive Molecules ◽

Successful Implementation ◽

Scale Production ◽

Exosome Biogenesis

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

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Deciphering the Mounting Complexity of the p53 Regulatory Network in Correlation to Long Non-Coding RNAs (lncRNAs) in Ovarian Cancer

Cells ◽

10.3390/cells9030527 ◽

2020 ◽

Vol 9 (3) ◽

pp. 527 ◽

Cited By ~ 10

Author(s):

Sonali Pal ◽

Manoj Garg ◽

Amit Kumar Pandey

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

Human Cancer ◽

Critical Role ◽

Functional Characterization ◽

Great Promise ◽

Altered Expression ◽

Disease Biology ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.

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Lysosomal Calcium Channels in Autophagy and Cancer

Cancers ◽

10.3390/cancers13061299 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1299

Author(s):

Yi Wu ◽

Peng Huang ◽

Xian-Ping Dong

Keyword(s):

Calcium Channels ◽

Cancer Progression ◽

Human Cancer ◽

Human Diseases ◽

Cellular Processes ◽

Cell Functions ◽

Multiple Cell ◽

Dependent Processes ◽

Intracellular Messenger

Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.

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