Abstract: The past decade has seen considerable excitement in the use of biological therapies in treating neoplastic disease. In particular, cancer immunotherapy and oncolytic virotherapy have emerged as two frontrunners in this regard with the first FDA approvals for agents in both categories being obtained in the last 5 years. It is becoming increasingly apparent that these two approaches are not mutually exclusive and that much of the therapeutic benefit obtained from the use of oncolytic viruses (OVs) is in fact the result of their immunotherapeutic function. Indeed, OVs have been shown to recruit and activate an antitumor immune response and much of the current work in this field centers around increasing this activity through strategies such as engineering genes for immunomodulators into OV backbones. Because of their broad immunostimulatory functions, OVs can also be rationally combined with a variety of other immunotherapeutic approaches including cancer vaccination strategies, adoptive cell transfer and checkpoint blockade. Therefore, while they are important therapeutics in their own right, the true power of OVs may lie in their ability to enhance the effectiveness of a wide range of immunotherapies.
Abstract: Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.
Abstract: Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Engineering the viruses to also express tumor-associated antigens (TAAs) allows them to simultaneously serve as therapeutic vaccines, targeting and amplifying an immune response to TAAs. Our group and others have shown that vaccinating intratumorally with a poxvirus that encodes TAAs, in addition to immune stimulatory molecules, can modulate the tumor microenvironment, overcome immune inhibitory pathways, and drive both local and systemic tumor specific immune responses.
Abstract: Oncolytic viruses (OVs) demonstrate the ability to replicate selectively in cancer cells, resulting in antitumor effects by a variety of mechanisms, including direct cell lysis and indirect cell death through immune-mediate host responses. Although the mechanisms of action of OVs are still not fully understood, major advances have been made in our understanding of how OVs function and interact with the host immune system, resulting in the recent FDA approval of the first OV for cancer therapy in the USA. This review provides an overview of the history of OVs, their selectivity for cancer cells, and their multifaceted mechanism of antitumor action, as well as strategies employed to augment selectivity and efficacy of OVs. OVs in combination with standard cancer therapies are also discussed, as well as a review of ongoing human clinical trials.
Abstract: Background: Caryota urens is a member of the Arecaceae family and a common plant in the Southeast Asian region. This plant has been reported as an anti-microbial agent in recent years. Thus, we aimed to find out the MIC (minimum inhibitory concentration) against different pathogenic microorganism. Methods: The leaves of C. urens were extracted and fractioned using different reagents (chloroform, n-hexane and carbon tetrachloride). Disc diffusion method was implemented for the assessment of in vitro anti-microbial potency (500 and 250 µg/disc). Result: The entire fraction showed good effect (with the zone of inhibition 19–25 mm) against both gram positive (Bacillus subtilis, Bacillus megaterium, Bacillus cereus, Sarina lutea) and gram negative (Vibrio mimicus, Shigella boydii, Escherichia coli, Pseudomonas aeruginosa) bacterial pathogens and fungal strains (Aspergillus niger, Saccharomyces cerevisiae). The plants also possess effective free radical scavenging potency with an IC50 of 130.32 µg/mL. Conclusion: This finding reflects a link between the presence of anti-oxidative material and a substantial anti-microbial activity, and substantiates all previous claims against C. urens.
Abstract: This review provides an overview of 50 years of basic and clinical research on an oncolytic avian virus, Newcastle Disease Virus (NDV), which has particular anti-neoplastic and immune stimulatory properties. Of special interest is the fact that this biological agent induces immunogenic cell death and systemic anti-tumor immunity. Furthermore, localized oncolytic virotherapy with NDV was shown to overcome systemic tumor resistance to immune checkpoint blockade immunotherapy. Clinical experience attests to low side effects and a high safety profile. This is due among others to the strong virus-induced type I interferon response. Other viral characteristics are lack of interaction with host cell DNA, lack of genetic recombination and independence of virus replication from cell proliferation. In this millennium, new recombinant strains of viruses are being produced with improved therapeutic properties. Clinical applications include single case observations, case series studies and Phase I to III studies.