The application of exosomes as a nanoscale cancer vaccine (original) (raw)
Related papers
Exosomes as Immunotheranostic Nanoparticles
Clinical Therapeutics, 2014
Background: Exosomes are small biological membrane vesicles that measure 30 to 100 nm in diameter. They are involved in a wide array of biological activities, such as cell-cell communication, signal transduction, transport of genetic materials, and modulation of immune response. Evidence indicates that they can be used as not only therapeutic agents targeted against disease but also diagnostic biomarkers for pathologic conditions. Objective: In this review, we endeavor to present exosomes as immunologic agents that can be used as pioneering cancer vaccines to prime the immune system and explicate their therapeutic and diagnostic capabilities. Methods: An extensive literature search for studies that involved the use of exosomes as immunotheranostic nanoparticles was conducted using PubMed, ISI Web of Knowledge, and Google Scholar. Clinical trials that involved exosomes were also compiled by searching the clinicaltrials.gov database. Results: In its therapeutic facet of application, exosomes can be used as vehicles for drug or gene delivery. These biological vesicles have been found to have excellent host biodistribution and biocompatibility, issues often presented with gene delivery vehicles. Diagnostically, exosomes may prove to be useful biomarkers that are able to surpass current setbacks of modern diagnostic testing, which include invasive methods. Finally, current evidence has implied that the use of exosomes could form the basis for the development of future cell-free cancer vaccines. Conclusion: Exosomes have numerous functions, and their double-edged features make the scope of their clinical applications, as both a diagnostic and therapeutic tool, immense.
Novel Cancer Treatment Using Engineered Exosomes to Disrupt Cancer’s Immune Escape
2020
Cancer is one of the leading causes of death in the United States . This disease has impacted 1 billions worldwide and has led to an ever-increasing burden on the healthcare system. Over the last couple of years, researchers have improved upon conventional cancer therapy that includes chemotherapy, radiation, and surgery. One novel approach is immunotherapy, which shows great potential because it has the ability to directly target cancerous cells . This is a viable treatment 2 because most cancers develop the ability to block immune pathways and evade the killer immune cells in what is known as cancer immune escape. One such pathway that is inhibited during the progression of specific cancers is the PD-L1 and PD-1 pathway thus inhibiting this pathway can be an effective treatment of advanced cancers . To improve upon the efficacy of certain 3 immunotherapies, we engineered a novel delivery method using exosomes to target this specific pathway. We focused on exosomes due to the nanov...
Harnessing the exosome-induced immune response for cancer immunotherapy
Seminars in Cancer Biology, 2014
In recent years exosomes have emerged as potent stimulators of immune responses and as agents for cancer therapy. Exosomes can carry a broad variety of immunostimulatory molecules depending on the cell of origin and in vitro culture conditions. Dendritic cell-derived exosomes (dexosomes) have been shown to carry NK cell activating ligands and can be loaded with antigen to activate invariant NKT cells and to induce antigen-specific T and B cell responses. Dexosomes have been investigated as therapeutic agents against cancer in two phase I clinical trials, with a phase II clinical trial currently ongoing. Dexosomes were well tolerated but therapeutic success and immune activation were limited.
Exosomes as Nanocarriers for Immunotherapy of Cancer and Inflammatory Diseases
Clinical immunology (Orlando, Fla.), 2015
Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APC), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many a...
The Dichotomy of Tumor Exosomes (TEX) in Cancer Immunity: Is It All in the ConTEXt?
Vaccines, 2015
Exosomes are virus-sized nanoparticles (30-130 nm) formed intracellularly as intravesicular bodies/intralumenal vesicles within maturing endosomes ("multivesicular bodies", MVBs). If MVBs fuse with the cell's plasma membrane, the interior vesicles may be released extracellularly, and are termed "exosomes". The protein cargo of exosomes consists of cytosolic, membrane, and extracellular proteins, along with membrane-derived lipids, and an extraordinary variety of nucleic acids. As such, exosomes reflect the status and identity of the parent cell, and are considered as tiny cellular surrogates. Because of this closely entwined relationship between exosome content and the source/status of the parental cell, conceivably exosomes could be used as vaccines against various pathologies, as they contain antigens associated with a given disease, e.g., cancer. Tumor-derived exosomes (TEX) have been shown to be potent anticancer vaccines in animal models, driving antigen...
Dendritic cell derived-exosomes: biology and clinical implementations
Journal of Leukocyte Biology, 2006
Exosomes are nanometer-sized membrane vesicles invaginating from multivesicular bodies and secreted from different cell types. They represent an "in vitro" discovery, but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition is unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation, or "Trojan horses" for viruses or prions. The potential of dendritic cell-derived exosomes (Dex) as cell-free cancer vaccines is addressed in this review. Lessons learned from the pioneering clinical trials allowed reassessment of the priming capacities of Dex in preclinical models, optimizing clinical protocols, and delineating novel, biological features of Dex in cancer patients. J. Leukoc. Biol. 80: 000 -000; 2006.
Exosomes: Versatile Nano Mediators of Immune Regulation
Cancers, 2019
One of many types of extracellular vesicles (EVs), exosomes are nanovesicle structures that are released by almost all living cells that can perform a wide range of critical biological functions. Exosomes play important roles in both normal and pathological conditions by regulating cell-cell communication in cancer, angiogenesis, cellular differentiation, osteogenesis, and inflammation. Exosomes are stable in vivo and they can regulate biological processes by transferring lipids, proteins, nucleic acids, and even entire signaling pathways through the circulation to cells at distal sites. Recent advances in the identification, production, and purification of exosomes have created opportunities to exploit these structures as novel drug delivery systems, modulators of cell signaling, mediators of antigen presentation, as well as biological targeting agents and diagnostic tools in cancer therapy. This review will examine the functions of immunocyte-derived exosomes and their roles in th...
Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer
Cellular Oncology
Background Exosomes are nanosized bio vesicles formed when multivesicular bodies and the plasma membrane merge and discharge into bodily fluids. They are well recognized for facilitating intercellular communication by transporting numerous biomolecules, including DNA, RNAs, proteins, and lipids, and have been implicated in varied diseases including cancer. Exosomes may be altered to transport a variety of therapeutic payloads, including as short interfering RNAs, antisense oligonucleotides, chemotherapeutic drugs, and immunological modulators, and can be directed to a specific target. Exosomes also possess the potential to act as a diagnostic biomarker in cancer, in addition to their therapeutic potential. Conclusion In this review, the physiological roles played by exosomes were summarized along with their biogenesis process. Different isolation techniques of exosomes including centrifugation-based, size-based, and polymer precipitation-based techniques have also been described in detail with a special focus on cancer therapeutic applications. The review also shed light on techniques of incubation of drugs with exosomes and their characterization methods covering the most advanced techniques. Myriad applications of exosomes in cancer as diagnostic biomarkers, drug delivery carriers, and chemoresistancerelated issues have been discussed at length. Furthermore, a brief overview of exosome-based anti-cancer vaccines and a few prominent challenges concerning exosomal delivery have been concluded at the end. Keywords Exosomes • cancer • Biomarkers • Isolation • Biogenesis Abbreviations ABCA-3 ATP binding cassette transporter-A3 ABCG-2 ATP binding cassette transporter-G2 AFM Atomic force microscopy AHSG Alpha-2-HS-glycoprotein CA-125 Cancer antigen-125 CAS-9 CRISPR associated protein 9 CIB1 Cryptochrome interacting basic helix-loop-helix1 CLIC/GEEC CDC-42 dependent clathrin-independent carrier /GPI-APenriched compartment
Cancer Research, 2011
MVA-BN-PRO (BN ImmunoTherapeutics) is a candidate immunotherapy product for the treatment of prostate cancer. It encodes 2 tumor-associated antigens, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP), and is derived from the highly attenuated modified vaccinia Ankara (MVA) virus stock known as MVA-BN. Past work has shown that the immunogenicity of antigens can be improved by targeting their localization to exosomes, which are small, 50-to 100-nm diameter vesicles secreted by most cell types. Exosome targeting is achieved by fusing the antigen to the C1C2 domain of the lactadherin protein. To test whether exosome targeting would improve the immunogenicity of PSA and PAP, 2 additional versions of MVA-BN-PRO were produced, targeting either PSA (MVA-BN-PSA-C1C2) or PAP (MVA-BN-PAP-C1C2) to exosomes, while leaving the second transgene untargeted. Treatment of mice with MVA-BN-PAP-C1C2 led to a striking increase in the immune response against PAP. Anti-PAP antibody titers developed more rapidly and reached levels that were 10-to 100-fold higher than those for mice treated with MVA-BN-PRO. Furthermore, treatment with MVA-BN-PAP-C1C2 increased the frequency of PAP-specific T cells 5-fold compared with mice treated with MVA-BN-PRO. These improvements translated into a greater frequency of tumor rejection in a PAP-expressing solid tumor model. Likewise, treatment with MVA-BN-PSA-C1C2 increased the antigenicity of PSA compared with treatment with MVA-BN-PRO and resulted in a trend of improved antitumor efficacy in a PSA-expressing tumor model. These experiments confirm that targeting antigen localization to exosomes is a viable approach for improving the therapeutic potential of MVA-BN-PRO in humans. Cancer Res; 71(15); 5235-44. Ó2011 AACR.